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TrueFoundry Receives Frost & Sullivan's 2026 Global Enterprise AI Control Plane Transformational Innovation Leadership Recognition for Enterprise AI Governance and Operational Excellence
SAN ANTONIO, Texas, Sept. 15 -- Frost and Sullivan, a provider of market research and analysis, growth strategy consulting and corporate training services, posted the following news release:
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TrueFoundry Receives Frost & Sullivan's 2026 Global Enterprise AI Control Plane Transformational Innovation Leadership Recognition for Enterprise AI Governance and Operational Excellence
The company is recognized for redefining enterprise AI operations through a unified control plane that enables secure, governed, observable, and scalable AI deployment.
SAN ANTONIO -- Frost & Sullivan is pleased to ... Show Full Article SAN ANTONIO, Texas, Sept. 15 -- Frost and Sullivan, a provider of market research and analysis, growth strategy consulting and corporate training services, posted the following news release: * * * TrueFoundry Receives Frost & Sullivan's 2026 Global Enterprise AI Control Plane Transformational Innovation Leadership Recognition for Enterprise AI Governance and Operational Excellence The company is recognized for redefining enterprise AI operations through a unified control plane that enables secure, governed, observable, and scalable AI deployment. SAN ANTONIO -- Frost & Sullivan is pleased toannounce that TrueFoundry has received the 2026 Global Enterprise AI Control Plane Transformational Innovation Leadership Recognition in the enterprise AI control plane industry. The recognition highlights TrueFoundry's differentiated approach to addressing fragmented enterprise AI ecosystems through a unified operational layer that brings together governance, security, observability, optimization, and agent lifecycle management, enabling organizations to operationalize AI with greater control, flexibility, and efficiency.
Frost & Sullivan evaluates companies through a rigorous benchmarking process across two core dimensions: Transformational Innovation and Customer Impact. After evaluating a number of vendors in the space, TrueFoundry emerged as the clear leader, demonstrating its ability to anticipate the evolving needs of enterprises ahead of existing solutions and translate its vision for a unified AI control plane into a scalable, enterprise-ready platform.
"The recognition highlights TrueFoundry's differentiated approach to addressing fragmented enterprise AI ecosystems through a unified operational layer that spans an organization's entire portfolio of AI agents and applications. By bringing together governance, security, observability, optimization, and agent lifecycle management, it enables organizations to operationalize AI with greater control, flexibility, and efficiency," said Arun Prasath, Principal Consultant, at Frost & Sullivan.
TrueFoundry has established an early architectural advantage in the emerging enterprise AI control plane market by investing in governed agent infrastructure, enterprise-wide AI governance, and interoperable gateway capabilities. Its platform supports organizations across North America, Latin America, Europe, Australia, and Asia-Pacific, with enterprise deployments spanning telecommunications, healthcare, banking, semiconductors, and other industries. TrueFoundry is used in production-facing workflows at Fortune 500s and vertical leaders such as Automation Anywhere, NetApp and Cox Communications.
Innovation remains central to TrueFoundry's approach. Its Enterprise AI Control Plane unifies governance across models, agents, and tools through the AI Gateway, incorporating an LLM Gateway, Model Context Protocol (MCP) Gateway, Agent Gateway, Agent Registry, and Skills Registry. Additionally, TrueForge by TrueFoundry is an open-source, vendor-neutral agent harness that lets users bring their own tools and models and build agents on their infrastructure. The platform's Kubernetes-native foundation supports multi-cloud, hybrid, on-premises, and air-gapped environments while enabling consistent security, compliance, observability, AI FinOps, and operational control.
"Everyone's focused on which model to use, but the harder problem is the layer underneath it, the one that decides whether you can govern it, afford it, and trust it in production. We built TrueFoundry as a centralized control plane for GenAI, one place where every model, agent, and tool call is governed. This recognition from Frost & Sullivan is validation about the importance of this control layer as enterprises scale their agentic AI use cases." Said Nikunj Bajaj, Co-founder and CEO at TrueFoundry
TrueFoundry's customer-centric approach further strengthens its market position. Structured proof-of-value engagements, rapid onboarding, dedicated enablement, engineering collaboration, training programs, and continuous product development help enterprises progress from initial AI experimentation to broader production adoption. Weekly feature releases and direct customer feedback enable the company to respond rapidly to evolving enterprise requirements. The company has also demonstrated measurable impact in production environments, including 3x faster time to value, 60% faster AI deployments, and 30% average cost optimization, all while operating at a scale of 1T+ tokens a day.
Frost & Sullivan commends TrueFoundry for establishing a strong standard in competitive strategy, technological innovation, execution, and market responsiveness. Its unified approach to AI governance, security, observability, sovereignty, and cost management is helping shape the emerging enterprise AI control plane category and enables organizations to scale AI responsibly.
Each year, Frost & Sullivan presents the Transformational Innovation Leadership Recognition to a company that demonstrates exceptional innovation and strategic execution, resulting in measurable improvements in customer value, competitive positioning, and market development. The recognition highlights forward-thinking organizations that are reshaping their industries through innovation and growth excellence.
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About TrueFoundry
TrueFoundry provides an enterprise-grade AI Gateway that encompasses an LLM Gateway, MCP Gateway, and Agent Gateway, enabling enterprises to securely connect, observe, and govern access to models, tools, guardrails, and agents from a single control plane. The AI Gateway enables agentic workloads that are secure, efficient, and future-safe through unified and composable connections across providers. TrueFoundry also includes TrueForge, an open-source, vendor-neutral agent harness that lets teams bring any model and tools on their own infrastructure.
TrueFoundry ensures enterprise-grade compliance with SOC 2, HIPAA, and ITAR standards. It is available as SaaS, on-prem, or air-gapped deployments, empowering organizations to build, deploy, and govern AI systems securely, efficiently, and on a future-safe stack.
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URL: TrueFoundry
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Original text here: https://www.frost.com/news/press-releases/truefoundry-receives-frost-sullivans-2026-global-enterprise-ai-control-plane-transformational-innovation-leadership-recognition-for-enterprise-ai-governance-and-operational-excellence/
[Category: BizConsulting]
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TrueFoundry Receives Frost & Sullivan's 2026 Global Enterprise AI Control Plane Transformational Innovation Leadership Recognition for Enterprise AI Governance and Operational Excellence
The company is recognized for redefining enterprise AI operations through a unified control plane that enables secure, governed, observable, and scalable AI deployment.
SAN ANTONIO -- Frost & Sullivan is pleased to ... Show Full Article SAN ANTONIO, Texas, Sept. 15 -- Frost and Sullivan, a provider of market research and analysis, growth strategy consulting and corporate training services, posted the following news release: * * * TrueFoundry Receives Frost & Sullivan's 2026 Global Enterprise AI Control Plane Transformational Innovation Leadership Recognition for Enterprise AI Governance and Operational Excellence The company is recognized for redefining enterprise AI operations through a unified control plane that enables secure, governed, observable, and scalable AI deployment. SAN ANTONIO -- Frost & Sullivan is pleased toannounce that TrueFoundry has received the 2026 Global Enterprise AI Control Plane Transformational Innovation Leadership Recognition in the enterprise AI control plane industry. The recognition highlights TrueFoundry's differentiated approach to addressing fragmented enterprise AI ecosystems through a unified operational layer that brings together governance, security, observability, optimization, and agent lifecycle management, enabling organizations to operationalize AI with greater control, flexibility, and efficiency.
Frost & Sullivan evaluates companies through a rigorous benchmarking process across two core dimensions: Transformational Innovation and Customer Impact. After evaluating a number of vendors in the space, TrueFoundry emerged as the clear leader, demonstrating its ability to anticipate the evolving needs of enterprises ahead of existing solutions and translate its vision for a unified AI control plane into a scalable, enterprise-ready platform.
"The recognition highlights TrueFoundry's differentiated approach to addressing fragmented enterprise AI ecosystems through a unified operational layer that spans an organization's entire portfolio of AI agents and applications. By bringing together governance, security, observability, optimization, and agent lifecycle management, it enables organizations to operationalize AI with greater control, flexibility, and efficiency," said Arun Prasath, Principal Consultant, at Frost & Sullivan.
TrueFoundry has established an early architectural advantage in the emerging enterprise AI control plane market by investing in governed agent infrastructure, enterprise-wide AI governance, and interoperable gateway capabilities. Its platform supports organizations across North America, Latin America, Europe, Australia, and Asia-Pacific, with enterprise deployments spanning telecommunications, healthcare, banking, semiconductors, and other industries. TrueFoundry is used in production-facing workflows at Fortune 500s and vertical leaders such as Automation Anywhere, NetApp and Cox Communications.
Innovation remains central to TrueFoundry's approach. Its Enterprise AI Control Plane unifies governance across models, agents, and tools through the AI Gateway, incorporating an LLM Gateway, Model Context Protocol (MCP) Gateway, Agent Gateway, Agent Registry, and Skills Registry. Additionally, TrueForge by TrueFoundry is an open-source, vendor-neutral agent harness that lets users bring their own tools and models and build agents on their infrastructure. The platform's Kubernetes-native foundation supports multi-cloud, hybrid, on-premises, and air-gapped environments while enabling consistent security, compliance, observability, AI FinOps, and operational control.
"Everyone's focused on which model to use, but the harder problem is the layer underneath it, the one that decides whether you can govern it, afford it, and trust it in production. We built TrueFoundry as a centralized control plane for GenAI, one place where every model, agent, and tool call is governed. This recognition from Frost & Sullivan is validation about the importance of this control layer as enterprises scale their agentic AI use cases." Said Nikunj Bajaj, Co-founder and CEO at TrueFoundry
TrueFoundry's customer-centric approach further strengthens its market position. Structured proof-of-value engagements, rapid onboarding, dedicated enablement, engineering collaboration, training programs, and continuous product development help enterprises progress from initial AI experimentation to broader production adoption. Weekly feature releases and direct customer feedback enable the company to respond rapidly to evolving enterprise requirements. The company has also demonstrated measurable impact in production environments, including 3x faster time to value, 60% faster AI deployments, and 30% average cost optimization, all while operating at a scale of 1T+ tokens a day.
Frost & Sullivan commends TrueFoundry for establishing a strong standard in competitive strategy, technological innovation, execution, and market responsiveness. Its unified approach to AI governance, security, observability, sovereignty, and cost management is helping shape the emerging enterprise AI control plane category and enables organizations to scale AI responsibly.
Each year, Frost & Sullivan presents the Transformational Innovation Leadership Recognition to a company that demonstrates exceptional innovation and strategic execution, resulting in measurable improvements in customer value, competitive positioning, and market development. The recognition highlights forward-thinking organizations that are reshaping their industries through innovation and growth excellence.
* * *
About TrueFoundry
TrueFoundry provides an enterprise-grade AI Gateway that encompasses an LLM Gateway, MCP Gateway, and Agent Gateway, enabling enterprises to securely connect, observe, and govern access to models, tools, guardrails, and agents from a single control plane. The AI Gateway enables agentic workloads that are secure, efficient, and future-safe through unified and composable connections across providers. TrueFoundry also includes TrueForge, an open-source, vendor-neutral agent harness that lets teams bring any model and tools on their own infrastructure.
TrueFoundry ensures enterprise-grade compliance with SOC 2, HIPAA, and ITAR standards. It is available as SaaS, on-prem, or air-gapped deployments, empowering organizations to build, deploy, and govern AI systems securely, efficiently, and on a future-safe stack.
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URL: TrueFoundry
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Original text here: https://www.frost.com/news/press-releases/truefoundry-receives-frost-sullivans-2026-global-enterprise-ai-control-plane-transformational-innovation-leadership-recognition-for-enterprise-ai-governance-and-operational-excellence/
[Category: BizConsulting]
Ropes & Gray Advises Appleby on Investment From New Mountain Capital to Accelerate Growth in Legal and Fiduciary Services
BOSTON, Massachusetts, Sept. 15 -- Ropes and Gray, a law firm, issued the following news:
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Ropes & Gray Advises Appleby on Investment from New Mountain Capital to Accelerate Growth in Legal and Fiduciary Services
Ropes & Gray has advised leading offshore legal and corporate services platform Appleby Global Group LLC ("Appleby") on a significant minority investment from affiliates of New Mountain Capital, LLC ("New Mountain"), a leading growth-oriented investment firm with approximately $60 billion in assets under management, to accelerate Appleby's growth strategy.
With a heritage of more ... Show Full Article BOSTON, Massachusetts, Sept. 15 -- Ropes and Gray, a law firm, issued the following news: * * * Ropes & Gray Advises Appleby on Investment from New Mountain Capital to Accelerate Growth in Legal and Fiduciary Services Ropes & Gray has advised leading offshore legal and corporate services platform Appleby Global Group LLC ("Appleby") on a significant minority investment from affiliates of New Mountain Capital, LLC ("New Mountain"), a leading growth-oriented investment firm with approximately $60 billion in assets under management, to accelerate Appleby's growth strategy. With a heritage of morethan 125 years, Appleby provides a seamlessly integrated offering of legal services, including both corporate and disputes services, and fiduciary services to the world's top financial institutions, investment managers, insurers, corporations, and select private clients. With more than 500 employees and approximately 200 attorneys serving clients across 11 offices in 8 jurisdictions, Appleby provides deep jurisdictional expertise and is a trusted adviser on the most complex, cross-border matters.
Under the leadership of Malcolm Moller, Appleby's Group Managing Partner, the firm has attracted many of the most accomplished attorneys in its markets. Appleby will continue to be led by its existing management team and partners, who will retain majority ownership of the business, and Malcolm Moller will take on the title of CEO of Appleby following the completion of this transaction. The law firm entities will remain owned and controlled by Appleby partners who are qualified in the relevant jurisdictions.
The Ropes & Gray team was led by private equity partners John Newton and Shona Ha, with support from associates Hayley Stokes-White, Michael Asprou, Alex Pattisson, Joshua Nicholson, and Fizaa Ahmed, and trainee associate Ned Robinson.
Additional support was provided by finance partner Greg Bauer and associates Liang Yinn Wong and Cary Chan, tax partners Chris Agnoli and David Saltzman and associate Luiza Galbraith, litigation & enforcement partners Lisa Kaltenbrunner and Sean Seelinger and associates Nathan Sekhar and Sienna Hewavidana, and data, privacy & cybersecurity partner Rohan Massey and associate Suzie Wilson.
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URL: Appleby Global Group
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Original text here: https://www.ropesgray.com/en/news-and-events/news/2026/09/ropes-gray-advises-appleby-on-investment-from-new-mountain-capital
[Category: BizLaw/Legal]
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Ropes & Gray Advises Appleby on Investment from New Mountain Capital to Accelerate Growth in Legal and Fiduciary Services
Ropes & Gray has advised leading offshore legal and corporate services platform Appleby Global Group LLC ("Appleby") on a significant minority investment from affiliates of New Mountain Capital, LLC ("New Mountain"), a leading growth-oriented investment firm with approximately $60 billion in assets under management, to accelerate Appleby's growth strategy.
With a heritage of more ... Show Full Article BOSTON, Massachusetts, Sept. 15 -- Ropes and Gray, a law firm, issued the following news: * * * Ropes & Gray Advises Appleby on Investment from New Mountain Capital to Accelerate Growth in Legal and Fiduciary Services Ropes & Gray has advised leading offshore legal and corporate services platform Appleby Global Group LLC ("Appleby") on a significant minority investment from affiliates of New Mountain Capital, LLC ("New Mountain"), a leading growth-oriented investment firm with approximately $60 billion in assets under management, to accelerate Appleby's growth strategy. With a heritage of morethan 125 years, Appleby provides a seamlessly integrated offering of legal services, including both corporate and disputes services, and fiduciary services to the world's top financial institutions, investment managers, insurers, corporations, and select private clients. With more than 500 employees and approximately 200 attorneys serving clients across 11 offices in 8 jurisdictions, Appleby provides deep jurisdictional expertise and is a trusted adviser on the most complex, cross-border matters.
Under the leadership of Malcolm Moller, Appleby's Group Managing Partner, the firm has attracted many of the most accomplished attorneys in its markets. Appleby will continue to be led by its existing management team and partners, who will retain majority ownership of the business, and Malcolm Moller will take on the title of CEO of Appleby following the completion of this transaction. The law firm entities will remain owned and controlled by Appleby partners who are qualified in the relevant jurisdictions.
The Ropes & Gray team was led by private equity partners John Newton and Shona Ha, with support from associates Hayley Stokes-White, Michael Asprou, Alex Pattisson, Joshua Nicholson, and Fizaa Ahmed, and trainee associate Ned Robinson.
Additional support was provided by finance partner Greg Bauer and associates Liang Yinn Wong and Cary Chan, tax partners Chris Agnoli and David Saltzman and associate Luiza Galbraith, litigation & enforcement partners Lisa Kaltenbrunner and Sean Seelinger and associates Nathan Sekhar and Sienna Hewavidana, and data, privacy & cybersecurity partner Rohan Massey and associate Suzie Wilson.
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URL: Appleby Global Group
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Original text here: https://www.ropesgray.com/en/news-and-events/news/2026/09/ropes-gray-advises-appleby-on-investment-from-new-mountain-capital
[Category: BizLaw/Legal]
Oracle: Environmental Health Expert Supports Project Jupiter Power Plan
REDWOOD SHORES, California, Sept. 15 -- Oracle, a developer of hardware and software products, issued the following news release:
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Environmental Health Expert Supports Project Jupiter Power Plan
Project Jupiter's updated energy plan is designed to reduce air emissions and water use while providing reliable power for the data center and delivering long-term benefits for Southern New Mexico.
In comments submitted to the New Mexico Environment Department, Dr. Christopher Ollson, an environmental-health scientist with more than 25 years of experience assessing facility emissions and public-health ... Show Full Article REDWOOD SHORES, California, Sept. 15 -- Oracle, a developer of hardware and software products, issued the following news release: * * * Environmental Health Expert Supports Project Jupiter Power Plan Project Jupiter's updated energy plan is designed to reduce air emissions and water use while providing reliable power for the data center and delivering long-term benefits for Southern New Mexico. In comments submitted to the New Mexico Environment Department, Dr. Christopher Ollson, an environmental-health scientist with more than 25 years of experience assessing facility emissions and public-healthimpacts, supported the air-permit application for the project's fuel-cell microgrid. Dr. Ollson was retained by Yucca Growth Infrastructure to review the application.
The project is located in the Paso del Norte border airshed, which includes southern Dona Ana County, El Paso, and Ciudad Juarez. Communities in this region have long faced air-quality challenges from sources including traffic, industry, and windblown dust.
Dr. Ollson's review found that Project Jupiter's proposed fuel-cell technology is a cleaner alternative to the natural-gas turbines and diesel backup generators previously planned for the site. Fuel cells generate electricity electrochemically rather than through combustion, substantially limiting the pollutants commonly associated with combustion-based power sources. "Because there is no flame and no combustion zone, the formation of these pollutants is largely avoided at the source." Dr. Ollson noted that the pollutants that burden the Paso del Norte border airshed "are precisely the ones avoided by fuel cell technology."
According to Dr. Ollson's review, the updated design is expected to reduce nitrogen oxide emissions by approximately 92 percent compared with the prior design. It would also avoid the need for diesel backup generators, which can be a source of particulate matter and nitrogen oxide emissions. "Because this community's airshed is already overburdened, the choice of energy-generating technology matters," Dr. Ollson wrote.
Dr. Ollson also notes that the updated design significantly reduces ongoing water use to a "negligible amount." Project Jupiter will use no public drinking water for data center cooling or fuel-cell operations. The systems require a one-time fill of approximately 11 million gallons of non-potable water; after that, ongoing maintenance is expected to require about 168,000 gallons per year. Averaged over 15 years, that is roughly the annual water use of nine U.S. households over the same time period. Oracle is also working with Arable to conserve more water than the project uses, and the project has committed $50 million to local water and wastewater infrastructure in Dona Ana County, with approximately 80 percent already funded.
Project Jupiter has generated nearly $80 million in state and county tax revenue and is expected to bring more than $4.7 billion in long-term economic impact to New Mexico. Nearly 700 New Mexico residents have worked onsite to date, and the project is on pace to create more than 7,000 construction jobs and 1,500 ongoing project-supported jobs once construction is complete.
Project Jupiter remains committed to developing responsibly, protecting New Mexico's resources, and engaging transparently with the community.
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Original text here: https://www.oracle.com/news/announcement/blog/environmental-healthexpert-supports-project-jupiter-power-plan-2026-09-14/
[Category: BizComputer Technology]
* * *
Environmental Health Expert Supports Project Jupiter Power Plan
Project Jupiter's updated energy plan is designed to reduce air emissions and water use while providing reliable power for the data center and delivering long-term benefits for Southern New Mexico.
In comments submitted to the New Mexico Environment Department, Dr. Christopher Ollson, an environmental-health scientist with more than 25 years of experience assessing facility emissions and public-health ... Show Full Article REDWOOD SHORES, California, Sept. 15 -- Oracle, a developer of hardware and software products, issued the following news release: * * * Environmental Health Expert Supports Project Jupiter Power Plan Project Jupiter's updated energy plan is designed to reduce air emissions and water use while providing reliable power for the data center and delivering long-term benefits for Southern New Mexico. In comments submitted to the New Mexico Environment Department, Dr. Christopher Ollson, an environmental-health scientist with more than 25 years of experience assessing facility emissions and public-healthimpacts, supported the air-permit application for the project's fuel-cell microgrid. Dr. Ollson was retained by Yucca Growth Infrastructure to review the application.
The project is located in the Paso del Norte border airshed, which includes southern Dona Ana County, El Paso, and Ciudad Juarez. Communities in this region have long faced air-quality challenges from sources including traffic, industry, and windblown dust.
Dr. Ollson's review found that Project Jupiter's proposed fuel-cell technology is a cleaner alternative to the natural-gas turbines and diesel backup generators previously planned for the site. Fuel cells generate electricity electrochemically rather than through combustion, substantially limiting the pollutants commonly associated with combustion-based power sources. "Because there is no flame and no combustion zone, the formation of these pollutants is largely avoided at the source." Dr. Ollson noted that the pollutants that burden the Paso del Norte border airshed "are precisely the ones avoided by fuel cell technology."
According to Dr. Ollson's review, the updated design is expected to reduce nitrogen oxide emissions by approximately 92 percent compared with the prior design. It would also avoid the need for diesel backup generators, which can be a source of particulate matter and nitrogen oxide emissions. "Because this community's airshed is already overburdened, the choice of energy-generating technology matters," Dr. Ollson wrote.
Dr. Ollson also notes that the updated design significantly reduces ongoing water use to a "negligible amount." Project Jupiter will use no public drinking water for data center cooling or fuel-cell operations. The systems require a one-time fill of approximately 11 million gallons of non-potable water; after that, ongoing maintenance is expected to require about 168,000 gallons per year. Averaged over 15 years, that is roughly the annual water use of nine U.S. households over the same time period. Oracle is also working with Arable to conserve more water than the project uses, and the project has committed $50 million to local water and wastewater infrastructure in Dona Ana County, with approximately 80 percent already funded.
Project Jupiter has generated nearly $80 million in state and county tax revenue and is expected to bring more than $4.7 billion in long-term economic impact to New Mexico. Nearly 700 New Mexico residents have worked onsite to date, and the project is on pace to create more than 7,000 construction jobs and 1,500 ongoing project-supported jobs once construction is complete.
Project Jupiter remains committed to developing responsibly, protecting New Mexico's resources, and engaging transparently with the community.
* * *
Original text here: https://www.oracle.com/news/announcement/blog/environmental-healthexpert-supports-project-jupiter-power-plan-2026-09-14/
[Category: BizComputer Technology]
Kohl's Expands Babies"R"Us Shops, Adds New Brands and Products
MENOMONEE FALLS, Wisconsin, Sept. 15 -- Kohl's, a department store retail company, issued the following news release:
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Kohl's Expands Babies"R"Us Shops, Adds New Brands and Products
Kohl's is adding dedicated Babies"R"Us shops to 56 additional stores this September, bringing a focused selection of baby gear, nursery items, and gifting essentials to more communities nationwide.
A Curated Destination for Growing Families
The new shops feature a thoughtful lineup of go-to products from popular brands, including strollers, car seats, feeding supplies, toys, and nursery decor. Additionally, ... Show Full Article MENOMONEE FALLS, Wisconsin, Sept. 15 -- Kohl's, a department store retail company, issued the following news release: * * * Kohl's Expands Babies"R"Us Shops, Adds New Brands and Products Kohl's is adding dedicated Babies"R"Us shops to 56 additional stores this September, bringing a focused selection of baby gear, nursery items, and gifting essentials to more communities nationwide. A Curated Destination for Growing Families The new shops feature a thoughtful lineup of go-to products from popular brands, including strollers, car seats, feeding supplies, toys, and nursery decor. Additionally,we are introducing a Babies"R"Us gifting assortment in all stores this fall.
What's New for Fall
- Exclusive Collection: The new Babies"R"Us Collection, available only at Kohl's, features bibs, blankets, and crib sheets with coordinated designs.
- New Brand Additions: Kohl's is introducing Millie Moon diapers, Hallmark gift sets, and seasonal stroller toys and books.
- Even More Affordable Gifting Options: Shoppers will now find even more baby gifts under $25, making it easier to pick up the perfect present for baby showers, first birthdays, and the holidays.
Whether shopping for a growing family or picking out a gift, Kohl's makes it easy to find the right baby products for every milestone. Shop the Babies"R"Us assortment at Kohl's stores nationwide and on Kohls.com.
Babies "R" Us shops opening at Kohl's in September:
- Arizona:
= Chandler - 1430 S Arizona Ave., Chandler, AZ
- California:
= Cerritos - 12821 Towne Center Dr., Cerritos, CA 90703
= City of Industry - 21818 Valley Blvd., City of Industry, CA 91789
= Corona - 470 Hidden Valley Pkwy., Corona, CA 92879
= Corona - 2489 Tuscany St., Corona, CA 92881
= Fontana - 14960 Summit Ave., Fontana, CA 92336
= Fresno - 3699 W Shaw Ave., Fresno, CA 93711
= Fullerton - 3204 Yorba Linda Blvd., Fullerton, CA 92831
= Huntington Beach - 9811 Adams Ave., Huntington Beach, CA 92646
= Monrovia - 504 W Huntington Dr., Monrovia, CA 91016
= Moorpark - 872 Los Angeles Ave., Moorpark, CA 93021
= Moreno Valley - 27200 Eucalyptus Ave., Moreno Valley, CA 92555
= Northridge - 8800 Corbin Ave., Northridge, CA 91324
= Oceanside - 3410 Marron Rd., Oceanside, CA 92056
= Ontario - 1051 N Milliken Ave., Ontario, CA 91764
= Redondo Beach - 1799 Hawthorne Blvd., Redondo Beach, CA 90278
= Riverside - 3520 Tyler St., Riverside, CA 92503
= Salinas - 1950 N Davis Rd., Salinas, CA 93907
= Santa Clarita - 19307 Golden Valley Rd., Santa Clarita, CA 91387
= Seal Beach - 12345 Seal Beach Blvd., Seal Beach, CA 90740
= Simi Valley - 2950 Tapo Canyon Rd., Simi Valley, CA 93063
= Sun Valley - 8501 Laurel Canyon Blvd., Sun Valley, CA 91352
= Temecula - 2085 Temecula Pkwy., Temecula, CA 92592
= Thousand Oaks - 1960 Newbury Rd., Newbury Park, CA 91320
= Valencia - 24200 Valencia Blvd., Valencia, CA 91355
= Yorba Linda -23001 Savi Ranch Pkwy., Yorba Linda, CA 92887
- Colorado:
= Brighton - 2425 Prairie Center Pkwy., Brighton, CO 80601
- Idaho:
= Nampa - 16566 N Marketplace Blvd., Nampa, ID 83687
- Illinois:
= Aurora - 4340 Fox Valley Center Dr., Aurora, IL 60504
= Mount Prospect - 1500 S Elmhurst Rd., Mount Prospect, IL 60056
- Nebraska:
= Papillion - 8909 S 71 St. Plaza, Papillion, NE 68133
- New Jersey:
= South Plainfield - 4971 Stelton Rd., South Plainfield, NJ 07080
- New York:
= Commack - 45 Crooked Hill Rd., Commack, NY 11725
= Deer Park - 409 Commack Rd., Deer Park, NY 11729
- Oregon:
= Hillsboro - 7360 NE Butler St., Hillsboro, OR 97124
- Pennsylvania:
= Blue Bell - 1301 Skippack Pike, Blue Bell, PA 19422
- Texas:
= Abilene - 4757 Southwest Dr., Abilene, TX 79606
= Amarillo - 2610 S Soncy Rd., Amarillo, TX 79124
= Atascocita - 7103 Farm to Market 1960 Rd. E, Atascocita, TX 77346
= Baytown - 6520 Garth Rd., Baytown, TX 77521
= Burleson - 1173 N Burleson Blvd., Burleson, TX 76028
= Conroe - 2808 Interstate 45 N, Conroe, TX 77303
= Conroe - 16640 Interstate 45 S, Conroe, TX 77384
= Copperfield - 7150 Barker Cypress Rd., Cypress, TX 77433
= Friendswood - 18178 Gulf Fwy., Friendswood, TX 77546
= Georgetown - 1019 W University Ave., Georgetown, TX 78628
= Houston - 1200 Fry Rd., Houston, TX 77084
= Houston - 22529 Tomball Pkwy., Houston, TX 77070
= Humble - 20755 US-59, Humble, TX 77338
= Lake Jackson - 201 TX-332, Lake Jackson, TX 77566
= League City - 2825 Gulf Fwy S, League City, TX 77573
= Meyerland - 4730 W. Bellfort St., Meyerland, TX 77035
= North Tomball - 14443 FM-2920 Rd., Tomball, TX 77377
= Pasadena - 5555 Fairmont Pkwy., Pasadena, TX 77505
= Richmond - 5550 W Grand Pkwy. S, Richmond, TX 77406
= Spring - 20614 Interstate 45 N, Spring, TX 77373
*/ Store locations and timing are subject to change
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Original text here: https://corporate.kohls.com/news/kohls-expands-babiesrus-shops-adds-new-brands-and-productsnbsp
[Category: BizConsumer Services]
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Kohl's Expands Babies"R"Us Shops, Adds New Brands and Products
Kohl's is adding dedicated Babies"R"Us shops to 56 additional stores this September, bringing a focused selection of baby gear, nursery items, and gifting essentials to more communities nationwide.
A Curated Destination for Growing Families
The new shops feature a thoughtful lineup of go-to products from popular brands, including strollers, car seats, feeding supplies, toys, and nursery decor. Additionally, ... Show Full Article MENOMONEE FALLS, Wisconsin, Sept. 15 -- Kohl's, a department store retail company, issued the following news release: * * * Kohl's Expands Babies"R"Us Shops, Adds New Brands and Products Kohl's is adding dedicated Babies"R"Us shops to 56 additional stores this September, bringing a focused selection of baby gear, nursery items, and gifting essentials to more communities nationwide. A Curated Destination for Growing Families The new shops feature a thoughtful lineup of go-to products from popular brands, including strollers, car seats, feeding supplies, toys, and nursery decor. Additionally,we are introducing a Babies"R"Us gifting assortment in all stores this fall.
What's New for Fall
- Exclusive Collection: The new Babies"R"Us Collection, available only at Kohl's, features bibs, blankets, and crib sheets with coordinated designs.
- New Brand Additions: Kohl's is introducing Millie Moon diapers, Hallmark gift sets, and seasonal stroller toys and books.
- Even More Affordable Gifting Options: Shoppers will now find even more baby gifts under $25, making it easier to pick up the perfect present for baby showers, first birthdays, and the holidays.
Whether shopping for a growing family or picking out a gift, Kohl's makes it easy to find the right baby products for every milestone. Shop the Babies"R"Us assortment at Kohl's stores nationwide and on Kohls.com.
Babies "R" Us shops opening at Kohl's in September:
- Arizona:
= Chandler - 1430 S Arizona Ave., Chandler, AZ
- California:
= Cerritos - 12821 Towne Center Dr., Cerritos, CA 90703
= City of Industry - 21818 Valley Blvd., City of Industry, CA 91789
= Corona - 470 Hidden Valley Pkwy., Corona, CA 92879
= Corona - 2489 Tuscany St., Corona, CA 92881
= Fontana - 14960 Summit Ave., Fontana, CA 92336
= Fresno - 3699 W Shaw Ave., Fresno, CA 93711
= Fullerton - 3204 Yorba Linda Blvd., Fullerton, CA 92831
= Huntington Beach - 9811 Adams Ave., Huntington Beach, CA 92646
= Monrovia - 504 W Huntington Dr., Monrovia, CA 91016
= Moorpark - 872 Los Angeles Ave., Moorpark, CA 93021
= Moreno Valley - 27200 Eucalyptus Ave., Moreno Valley, CA 92555
= Northridge - 8800 Corbin Ave., Northridge, CA 91324
= Oceanside - 3410 Marron Rd., Oceanside, CA 92056
= Ontario - 1051 N Milliken Ave., Ontario, CA 91764
= Redondo Beach - 1799 Hawthorne Blvd., Redondo Beach, CA 90278
= Riverside - 3520 Tyler St., Riverside, CA 92503
= Salinas - 1950 N Davis Rd., Salinas, CA 93907
= Santa Clarita - 19307 Golden Valley Rd., Santa Clarita, CA 91387
= Seal Beach - 12345 Seal Beach Blvd., Seal Beach, CA 90740
= Simi Valley - 2950 Tapo Canyon Rd., Simi Valley, CA 93063
= Sun Valley - 8501 Laurel Canyon Blvd., Sun Valley, CA 91352
= Temecula - 2085 Temecula Pkwy., Temecula, CA 92592
= Thousand Oaks - 1960 Newbury Rd., Newbury Park, CA 91320
= Valencia - 24200 Valencia Blvd., Valencia, CA 91355
= Yorba Linda -23001 Savi Ranch Pkwy., Yorba Linda, CA 92887
- Colorado:
= Brighton - 2425 Prairie Center Pkwy., Brighton, CO 80601
- Idaho:
= Nampa - 16566 N Marketplace Blvd., Nampa, ID 83687
- Illinois:
= Aurora - 4340 Fox Valley Center Dr., Aurora, IL 60504
= Mount Prospect - 1500 S Elmhurst Rd., Mount Prospect, IL 60056
- Nebraska:
= Papillion - 8909 S 71 St. Plaza, Papillion, NE 68133
- New Jersey:
= South Plainfield - 4971 Stelton Rd., South Plainfield, NJ 07080
- New York:
= Commack - 45 Crooked Hill Rd., Commack, NY 11725
= Deer Park - 409 Commack Rd., Deer Park, NY 11729
- Oregon:
= Hillsboro - 7360 NE Butler St., Hillsboro, OR 97124
- Pennsylvania:
= Blue Bell - 1301 Skippack Pike, Blue Bell, PA 19422
- Texas:
= Abilene - 4757 Southwest Dr., Abilene, TX 79606
= Amarillo - 2610 S Soncy Rd., Amarillo, TX 79124
= Atascocita - 7103 Farm to Market 1960 Rd. E, Atascocita, TX 77346
= Baytown - 6520 Garth Rd., Baytown, TX 77521
= Burleson - 1173 N Burleson Blvd., Burleson, TX 76028
= Conroe - 2808 Interstate 45 N, Conroe, TX 77303
= Conroe - 16640 Interstate 45 S, Conroe, TX 77384
= Copperfield - 7150 Barker Cypress Rd., Cypress, TX 77433
= Friendswood - 18178 Gulf Fwy., Friendswood, TX 77546
= Georgetown - 1019 W University Ave., Georgetown, TX 78628
= Houston - 1200 Fry Rd., Houston, TX 77084
= Houston - 22529 Tomball Pkwy., Houston, TX 77070
= Humble - 20755 US-59, Humble, TX 77338
= Lake Jackson - 201 TX-332, Lake Jackson, TX 77566
= League City - 2825 Gulf Fwy S, League City, TX 77573
= Meyerland - 4730 W. Bellfort St., Meyerland, TX 77035
= North Tomball - 14443 FM-2920 Rd., Tomball, TX 77377
= Pasadena - 5555 Fairmont Pkwy., Pasadena, TX 77505
= Richmond - 5550 W Grand Pkwy. S, Richmond, TX 77406
= Spring - 20614 Interstate 45 N, Spring, TX 77373
*/ Store locations and timing are subject to change
* * *
Original text here: https://corporate.kohls.com/news/kohls-expands-babiesrus-shops-adds-new-brands-and-productsnbsp
[Category: BizConsumer Services]
Johnson & Johnson's 2026 Oncology Care Index Finds Community Oncologists Confident in AI's Promise, But Practical Adoption Still Lags
RARITAN, New Jersey, Sept. 15 -- Johnson and Johnson Innovative Medicine issued the following news release:
* * *
Johnson & Johnson's 2026 Oncology Care Index Finds Community Oncologists Confident in AI's Promise, but Practical Adoption Still Lags
* Reported AI adoption in oncology has increased from 19% of healthcare providers across all practice
settings in 2025 to 49% of community oncologists specifically in 2026
* Meanwhile use of advanced tools like predictive models remains low, at just 19%, revealing a gap
between adoption and deeper implementation
HORSHAM, PA, September 14, 2026 ... Show Full Article RARITAN, New Jersey, Sept. 15 -- Johnson and Johnson Innovative Medicine issued the following news release: * * * Johnson & Johnson's 2026 Oncology Care Index Finds Community Oncologists Confident in AI's Promise, but Practical Adoption Still Lags * Reported AI adoption in oncology has increased from 19% of healthcare providers across all practice settings in 2025 to 49% of community oncologists specifically in 2026 * Meanwhile use of advanced tools like predictive models remains low, at just 19%, revealing a gap between adoption and deeper implementation HORSHAM, PA, September 14, 2026- Johnson & Johnson (NYSE: JNJ) today released findings from its 2026 Oncology Care Index, a comprehensive survey conducted in partnership with The Harris Poll to look at the state of cancer delivery in the U.S. This year, the Index surveyed 200+ community oncologists and practice administrators across the United States and revealed a striking paradox in community oncology: AI use is accelerating and confidence in AI among oncologists is high, but advanced implementation remains limited. Just over 8 in 10 community oncologists surveyed (83%) believe AI can help make cancer care more accessible for more patients, yet only 19% are currently using AI-powered predictive models. The barrier is not a lack of awareness or openness, but a lack of the tools, training and infrastructure needed to use AI confidently and consistently in practice./1
Community oncology practices form the backbone of cancer care, caring for nearly 85 percent of people living with cancer in the U.S./2 Johnson & Johnson is sharing these findings to identify where implementation challenges persist and what it will take to help community practices translate innovation into meaningful patient impact.
The survey revealed three key themes about AI implementation in community oncology:
* Adoption must move from early use to sustained impact. Nearly half of community oncologists surveyed reported actively using AI tools - 49%, up from 19% of healthcare providers in all practice settings in 2025.
* Familiarity and confidence are high, but usage lags. More than three-quarters of surveyed community oncologists are familiar with AI-powered predictive models and feel confident in their ability to use AI to inform treatment decisions (79%), yet 19% are currently using these tools.
* Practical enablement is now the priority. Most community oncologists say more education and advocacy are needed to accelerate AI adoption. But the real barriers are structural: lack of reimbursement for AI-powered tools (44%), limited formal training (43%) and insufficient funding (41%).
"The Oncology Care Index shows that community oncologists are not waiting to be invited to the AI conversation. We are already in it, but what we need now are the tools, the training, and the structural support to move from early experimentation to consistent, confident practice," said Dr. Stephen (Fred) Divers, Chief Medical Officer at American Oncology Network. "These findings give us the evidence base to make that case to payers, policymakers, and health systems, so that patients in the smallest communities can benefit from the same innovations as those in large cities or academic centers."
Community practices are ready to lead: 78% of surveyed community oncologists, and 96% of surveyed administrators say community oncology practices are uniquely positioned to accelerate access to new cancer treatments. But payer barriers remain a real obstacle: 97% say they delay or prevent patients from receiving the therapies they believe are most appropriate.
Three opportunity areas emerged where targeted action can help turn readiness into impact:
1. Helping to solve cancer research's participation problem: 60% of community oncologists surveyed say their practice offers limited trial options. Reimagining trials around real-world patient education, an approach 94% say would boost participation, can make research more accessible where patients already receive care.
2. Scaling AI's early momentum: AI-adopting practices report greater confidence in their ability to expand care and lead their communities forward. Investing in training, reimbursement pathways and implementation support now will determine whether AI's early momentum becomes lasting impact.
3. Closing the immunotherapies confidence gap: More than 9 in 10 community oncologists surveyed feel their practice is comfortable managing (92%) and is equipped to offer (94%) new immunotherapies, but fewer are very comfortable (43%) or very equipped (35%). Staff training and expertise to implement immunotherapies; financial and reimbursement resources; and infrastructure to develop adverse event management protocols were the top-cited barrier (38%; 38%; 37% respectively).
"Last year, the Oncology Care Index established a baseline. Year two tells us something more urgent: the gap between what community oncologists believe AI can do and what they can actually do with it today isn't closing on its own," said Kevin Hamill, Company Group Chairman, Johnson & Johnson Innovative Medicine North America. "That's not a confidence problem: it's a systems problem, which is why we're investing directly in areas that can help move them from readiness to real impact."
To accelerate progress on these priorities, J&J is issuing a request for proposal designed to support not for profit organizations working in cancer care to implement solutions that address the key barriers identified in the 2026 Oncology Care Index.
J&J is also advancing other solutions to help community settings, including Medical Affairs Implementation Science Grants supporting clinical trial infrastructure, developing programs that scale pathways for delivering advanced immunotherapies closer to home, and collaborating with NCODA (Network for Collaborative Oncology Development and Advancement) through Project Community to identify and overcome key care gaps to raise quality of and access to innovation. In addition, J&J is supporting AI upskilling of the U.S. rural health workforce in a coordinated investment with Google.org.
Learn more about the Oncology Care Index and how J&J is driving change at:
https://www.jnj.com/innovativemedicine/oncologycareindex.
Johnson & Johnson's Oncology Care Index Survey Methodology
Johnson & Johnson's Oncology Care Index is a survey that asked healthcare professionals working in oncology to identify the challenges they face in delivering the best care for their patients. The research was conducted online in the United States by The Harris Poll on behalf of Johnson & Johnson among:
* 109 community oncologists age 18+ who are duly licensed, and whose primary medical specialty was in hematology/oncology and have treated patients with solid tumor and hematologic cancer in a community setting.
* 100 practice administrators/managers age 18+ employed in healthcare at a practice specializing in hematology/oncology in a community setting that treats hematologic and solid tumor cancer.
The survey was conducted May 21-July 6, 2026. Healthcare professionals and physicians who qualified for and successfully completed the survey were compensated for their participation.
Raw data are not weighted and therefore only representative of the individuals who completed the survey. Respondents for this survey were selected from among those who have agreed to participate in our surveys.
The sampling precision of Harris online polls is measured by using a Bayesian credible interval. For this study, the sample data are accurate to within +- 9.6 percentage (for practice administrators and managers) and within +- 9.3 percentage (for community oncologists) points using a 95% confidence level. This credible interval will be wider among subsets of the surveyed population of interest.
* * *
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at https://www.jnj.com/innovativemedicine/. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc., are both Johnson & Johnson companies.
* * *
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com, https://investor.jnj.com, or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.
* * *
Footnotes
"Dr. Stephen (Fred) Divers has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work."
1/ Johnson & Johnson & The Harris Poll. (2026)
2/ Association of Cancer Care Centers. ACCC Community Oncology Research Institute. Available at: https://www.accc-cancer.org/education and-resources/research/accc-community-oncology-research-institute.
* * *
Original text here: https://www.jnj.com/media-center/press-releases/johnson-johnsons-2026-oncology-care-index-finds-community-oncologists-confident-in-ais-promise-but-practical-adoption-still-lags
[Category: BizPharmaceuticals]
* * *
Johnson & Johnson's 2026 Oncology Care Index Finds Community Oncologists Confident in AI's Promise, but Practical Adoption Still Lags
* Reported AI adoption in oncology has increased from 19% of healthcare providers across all practice
settings in 2025 to 49% of community oncologists specifically in 2026
* Meanwhile use of advanced tools like predictive models remains low, at just 19%, revealing a gap
between adoption and deeper implementation
HORSHAM, PA, September 14, 2026 ... Show Full Article RARITAN, New Jersey, Sept. 15 -- Johnson and Johnson Innovative Medicine issued the following news release: * * * Johnson & Johnson's 2026 Oncology Care Index Finds Community Oncologists Confident in AI's Promise, but Practical Adoption Still Lags * Reported AI adoption in oncology has increased from 19% of healthcare providers across all practice settings in 2025 to 49% of community oncologists specifically in 2026 * Meanwhile use of advanced tools like predictive models remains low, at just 19%, revealing a gap between adoption and deeper implementation HORSHAM, PA, September 14, 2026- Johnson & Johnson (NYSE: JNJ) today released findings from its 2026 Oncology Care Index, a comprehensive survey conducted in partnership with The Harris Poll to look at the state of cancer delivery in the U.S. This year, the Index surveyed 200+ community oncologists and practice administrators across the United States and revealed a striking paradox in community oncology: AI use is accelerating and confidence in AI among oncologists is high, but advanced implementation remains limited. Just over 8 in 10 community oncologists surveyed (83%) believe AI can help make cancer care more accessible for more patients, yet only 19% are currently using AI-powered predictive models. The barrier is not a lack of awareness or openness, but a lack of the tools, training and infrastructure needed to use AI confidently and consistently in practice./1
Community oncology practices form the backbone of cancer care, caring for nearly 85 percent of people living with cancer in the U.S./2 Johnson & Johnson is sharing these findings to identify where implementation challenges persist and what it will take to help community practices translate innovation into meaningful patient impact.
The survey revealed three key themes about AI implementation in community oncology:
* Adoption must move from early use to sustained impact. Nearly half of community oncologists surveyed reported actively using AI tools - 49%, up from 19% of healthcare providers in all practice settings in 2025.
* Familiarity and confidence are high, but usage lags. More than three-quarters of surveyed community oncologists are familiar with AI-powered predictive models and feel confident in their ability to use AI to inform treatment decisions (79%), yet 19% are currently using these tools.
* Practical enablement is now the priority. Most community oncologists say more education and advocacy are needed to accelerate AI adoption. But the real barriers are structural: lack of reimbursement for AI-powered tools (44%), limited formal training (43%) and insufficient funding (41%).
"The Oncology Care Index shows that community oncologists are not waiting to be invited to the AI conversation. We are already in it, but what we need now are the tools, the training, and the structural support to move from early experimentation to consistent, confident practice," said Dr. Stephen (Fred) Divers, Chief Medical Officer at American Oncology Network. "These findings give us the evidence base to make that case to payers, policymakers, and health systems, so that patients in the smallest communities can benefit from the same innovations as those in large cities or academic centers."
Community practices are ready to lead: 78% of surveyed community oncologists, and 96% of surveyed administrators say community oncology practices are uniquely positioned to accelerate access to new cancer treatments. But payer barriers remain a real obstacle: 97% say they delay or prevent patients from receiving the therapies they believe are most appropriate.
Three opportunity areas emerged where targeted action can help turn readiness into impact:
1. Helping to solve cancer research's participation problem: 60% of community oncologists surveyed say their practice offers limited trial options. Reimagining trials around real-world patient education, an approach 94% say would boost participation, can make research more accessible where patients already receive care.
2. Scaling AI's early momentum: AI-adopting practices report greater confidence in their ability to expand care and lead their communities forward. Investing in training, reimbursement pathways and implementation support now will determine whether AI's early momentum becomes lasting impact.
3. Closing the immunotherapies confidence gap: More than 9 in 10 community oncologists surveyed feel their practice is comfortable managing (92%) and is equipped to offer (94%) new immunotherapies, but fewer are very comfortable (43%) or very equipped (35%). Staff training and expertise to implement immunotherapies; financial and reimbursement resources; and infrastructure to develop adverse event management protocols were the top-cited barrier (38%; 38%; 37% respectively).
"Last year, the Oncology Care Index established a baseline. Year two tells us something more urgent: the gap between what community oncologists believe AI can do and what they can actually do with it today isn't closing on its own," said Kevin Hamill, Company Group Chairman, Johnson & Johnson Innovative Medicine North America. "That's not a confidence problem: it's a systems problem, which is why we're investing directly in areas that can help move them from readiness to real impact."
To accelerate progress on these priorities, J&J is issuing a request for proposal designed to support not for profit organizations working in cancer care to implement solutions that address the key barriers identified in the 2026 Oncology Care Index.
J&J is also advancing other solutions to help community settings, including Medical Affairs Implementation Science Grants supporting clinical trial infrastructure, developing programs that scale pathways for delivering advanced immunotherapies closer to home, and collaborating with NCODA (Network for Collaborative Oncology Development and Advancement) through Project Community to identify and overcome key care gaps to raise quality of and access to innovation. In addition, J&J is supporting AI upskilling of the U.S. rural health workforce in a coordinated investment with Google.org.
Learn more about the Oncology Care Index and how J&J is driving change at:
https://www.jnj.com/innovativemedicine/oncologycareindex.
Johnson & Johnson's Oncology Care Index Survey Methodology
Johnson & Johnson's Oncology Care Index is a survey that asked healthcare professionals working in oncology to identify the challenges they face in delivering the best care for their patients. The research was conducted online in the United States by The Harris Poll on behalf of Johnson & Johnson among:
* 109 community oncologists age 18+ who are duly licensed, and whose primary medical specialty was in hematology/oncology and have treated patients with solid tumor and hematologic cancer in a community setting.
* 100 practice administrators/managers age 18+ employed in healthcare at a practice specializing in hematology/oncology in a community setting that treats hematologic and solid tumor cancer.
The survey was conducted May 21-July 6, 2026. Healthcare professionals and physicians who qualified for and successfully completed the survey were compensated for their participation.
Raw data are not weighted and therefore only representative of the individuals who completed the survey. Respondents for this survey were selected from among those who have agreed to participate in our surveys.
The sampling precision of Harris online polls is measured by using a Bayesian credible interval. For this study, the sample data are accurate to within +- 9.6 percentage (for practice administrators and managers) and within +- 9.3 percentage (for community oncologists) points using a 95% confidence level. This credible interval will be wider among subsets of the surveyed population of interest.
* * *
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at https://www.jnj.com/innovativemedicine/. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc., are both Johnson & Johnson companies.
* * *
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com, https://investor.jnj.com, or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.
* * *
Footnotes
"Dr. Stephen (Fred) Divers has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work."
1/ Johnson & Johnson & The Harris Poll. (2026)
2/ Association of Cancer Care Centers. ACCC Community Oncology Research Institute. Available at: https://www.accc-cancer.org/education and-resources/research/accc-community-oncology-research-institute.
* * *
Original text here: https://www.jnj.com/media-center/press-releases/johnson-johnsons-2026-oncology-care-index-finds-community-oncologists-confident-in-ais-promise-but-practical-adoption-still-lags
[Category: BizPharmaceuticals]
GE Vernova to Supply 29.4 MW of Wind Capacity for Eurus Energy's Hiyamizutouge Project in Japan
CAMBRIDGE, Massachusetts, Sept. 15 -- G.E. Vernova, an energy company, posted the following news release:
* * *
GE Vernova to supply 29.4 MW of wind capacity for Eurus Energy's Hiyamizutouge Project in Japan
- Order features 4.2MW workhorse turbines designed to deliver reliable performance in Japan's unique wind conditions
- Deal accelerates GE Vernova's momentum in Japan's expanding wind market
- GE Vernova technology powers approximately 50% of the country's installed heavy-duty gas turbine capacity and 25% of its onshore wind capacity.
- Workhorse strategy features standardized, industrialized ... Show Full Article CAMBRIDGE, Massachusetts, Sept. 15 -- G.E. Vernova, an energy company, posted the following news release: * * * GE Vernova to supply 29.4 MW of wind capacity for Eurus Energy's Hiyamizutouge Project in Japan - Order features 4.2MW workhorse turbines designed to deliver reliable performance in Japan's unique wind conditions - Deal accelerates GE Vernova's momentum in Japan's expanding wind market - GE Vernova technology powers approximately 50% of the country's installed heavy-duty gas turbine capacity and 25% of its onshore wind capacity. - Workhorse strategy features standardized, industrializedmachines engineered for repeatable execution and long-term reliability
TOKYO, Japan - GE Vernova (NYSE: GEV) announced today that its Onshore Wind business has signed an agreement/* with Eurus Energy Holdings Corporation (Eurus Energy) to supply seven 4.2 MW-117m/** wind turbines for the 29.4 MW Eurus Hiyamizutouge Wind Farm in Mutsu City and Higashidori Village, Aomori Prefecture, Japan. The deal includes a two-year service agreement with an option for a two-year extension.
The 4.2 MW-117m turbines are part of GE Vernova's workhorse 4 MW platform, with over 2 million operating hours, this turbine has been specifically engineered to deliver high-output, reliable performance in Japan's unique wind conditions.
"We are pleased to partner once again with Eurus Energy to bring the Hiyamizutouge project to life," said Gilan Sabatier, Chief Commercial Officer of Onshore Wind, International Markets at GE Vernova. "Our 4 MW platform is well-suited to the Japanese landscape, offering the durability and efficiency required to maximize the country's wind potential. GE Vernova technology currently powers 25% of Japan's installed wind capacity, and we remain dedicated to supporting the nation's energy transition."
Masaru Akiyoshi, Representative Director and Executive Vice President, Eurus Energy said, "We are pleased to once again partner with GE Vernova on a renewable energy project in Japan. We are grateful to the people of Mutsu City and Higashidori Village, the administrative agencies, and all stakeholders for their support. We look forward to building this new wind farm in Aomori together and contributing to Japan's renewable energy goals through our continued collaboration".
This project contributes to Japan's ambitious goal of generating 36-38% of its electricity from renewable sources by 2030. GE Vernova and Japan's Ministry of Economy, Trade and Industry (METI) launched a joint focus group on June 10, 2025, aimed at addressing challenges and opportunities and deepening collaboration in energy security and innovation.
This announcement follows a period of strong momentum for GE Vernova in Japan, where the company has secured 339 MW of orders in 2025 across a diverse customer base, including established utilities and emerging independent power producers. GE Vernova and its technologies contribute significantly to Japan's overall electric capacity, accounting for around 50% of the country's installed Heavy-Duty Gas Turbine power generation capacity and 25% of the country's onshore wind capacity.
GE Vernova's Wind segment's portfolio reflects a deliberate workhorse strategy -- standardized, industrialized machines engineered for repeatable execution and long-term reliability. With more than 59,000 turbines operating globally, its experience informs every product it designs, manufactures, and deploys.
* * *
About GE Vernova
GE Vernova Inc. (NYSE: GEV) is a purpose-built global energy company that includes Power, Electrification and Wind segments and is supported by its accelerator businesses. Building on over 130 years of experience tackling the world's challenges, GE Vernova is uniquely positioned to help lead the energy transition by continuing to electrify the world while simultaneously working to decarbonize it. GE Vernova helps customers power economies and deliver electricity that is vital to health, safety, security, and improved quality of life. GE Vernova is headquartered in Cambridge, Massachusetts, U.S., with approximately 85,000 employees across approximately 100 countries around the world. Supported by the Company's purpose, The Energy to Change the World, GE Vernova technology helps deliver a more affordable, reliable, sustainable, and secure energy future.
GE Vernova's Wind segment is focused on delivering a suite of wind products and services to help accelerate a new era of energy by harnessing the power of wind. Technologies provided to customers include the next generation high efficiency 3-megawatt onshore wind turbine and the Haliade-X offshore wind turbine platform, as well as maintenance solutions and life extension optionality.
* * *
Forward-Looking Statements
This document contains forward-looking statements - that is, statements related to future events that by their nature address matters that are, to different degrees, uncertain. These forward-looking statements often address GE Vernova's expected future business and financial performance and financial condition, and the expected performance of its products, the impact of its services and the results they may generate or produce, and often contain words such as "expect," "anticipate," "intend," "plan," "believe," "seek," "see," "will," "would," "estimate," "forecast," "target," "preliminary," or "range." Forward-looking statements by their nature address matters that are, to different degrees, uncertain, such as statements about planned and potential transactions, investments or projects and their expected results and the impacts of macroeconomic and market conditions and volatility on the Company's business operations, financial results and financial position and on the global supply chain and world economy.
* * *
Notes to editor:
*/ The order was booked in the second quarter of 2026.
**/ GE Vernova's 4.2MW turbine with a 117-meter rotor is referred to as the 4.2MW-117m.
* * *
Original text here: https://www.gevernova.com/news/press-releases/ge-vernova-supply-294-mw-wind-capacity-eurus-energys-hiyamizutouge-project-japan
[Category: BizEnergy]
* * *
GE Vernova to supply 29.4 MW of wind capacity for Eurus Energy's Hiyamizutouge Project in Japan
- Order features 4.2MW workhorse turbines designed to deliver reliable performance in Japan's unique wind conditions
- Deal accelerates GE Vernova's momentum in Japan's expanding wind market
- GE Vernova technology powers approximately 50% of the country's installed heavy-duty gas turbine capacity and 25% of its onshore wind capacity.
- Workhorse strategy features standardized, industrialized ... Show Full Article CAMBRIDGE, Massachusetts, Sept. 15 -- G.E. Vernova, an energy company, posted the following news release: * * * GE Vernova to supply 29.4 MW of wind capacity for Eurus Energy's Hiyamizutouge Project in Japan - Order features 4.2MW workhorse turbines designed to deliver reliable performance in Japan's unique wind conditions - Deal accelerates GE Vernova's momentum in Japan's expanding wind market - GE Vernova technology powers approximately 50% of the country's installed heavy-duty gas turbine capacity and 25% of its onshore wind capacity. - Workhorse strategy features standardized, industrializedmachines engineered for repeatable execution and long-term reliability
TOKYO, Japan - GE Vernova (NYSE: GEV) announced today that its Onshore Wind business has signed an agreement/* with Eurus Energy Holdings Corporation (Eurus Energy) to supply seven 4.2 MW-117m/** wind turbines for the 29.4 MW Eurus Hiyamizutouge Wind Farm in Mutsu City and Higashidori Village, Aomori Prefecture, Japan. The deal includes a two-year service agreement with an option for a two-year extension.
The 4.2 MW-117m turbines are part of GE Vernova's workhorse 4 MW platform, with over 2 million operating hours, this turbine has been specifically engineered to deliver high-output, reliable performance in Japan's unique wind conditions.
"We are pleased to partner once again with Eurus Energy to bring the Hiyamizutouge project to life," said Gilan Sabatier, Chief Commercial Officer of Onshore Wind, International Markets at GE Vernova. "Our 4 MW platform is well-suited to the Japanese landscape, offering the durability and efficiency required to maximize the country's wind potential. GE Vernova technology currently powers 25% of Japan's installed wind capacity, and we remain dedicated to supporting the nation's energy transition."
Masaru Akiyoshi, Representative Director and Executive Vice President, Eurus Energy said, "We are pleased to once again partner with GE Vernova on a renewable energy project in Japan. We are grateful to the people of Mutsu City and Higashidori Village, the administrative agencies, and all stakeholders for their support. We look forward to building this new wind farm in Aomori together and contributing to Japan's renewable energy goals through our continued collaboration".
This project contributes to Japan's ambitious goal of generating 36-38% of its electricity from renewable sources by 2030. GE Vernova and Japan's Ministry of Economy, Trade and Industry (METI) launched a joint focus group on June 10, 2025, aimed at addressing challenges and opportunities and deepening collaboration in energy security and innovation.
This announcement follows a period of strong momentum for GE Vernova in Japan, where the company has secured 339 MW of orders in 2025 across a diverse customer base, including established utilities and emerging independent power producers. GE Vernova and its technologies contribute significantly to Japan's overall electric capacity, accounting for around 50% of the country's installed Heavy-Duty Gas Turbine power generation capacity and 25% of the country's onshore wind capacity.
GE Vernova's Wind segment's portfolio reflects a deliberate workhorse strategy -- standardized, industrialized machines engineered for repeatable execution and long-term reliability. With more than 59,000 turbines operating globally, its experience informs every product it designs, manufactures, and deploys.
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About GE Vernova
GE Vernova Inc. (NYSE: GEV) is a purpose-built global energy company that includes Power, Electrification and Wind segments and is supported by its accelerator businesses. Building on over 130 years of experience tackling the world's challenges, GE Vernova is uniquely positioned to help lead the energy transition by continuing to electrify the world while simultaneously working to decarbonize it. GE Vernova helps customers power economies and deliver electricity that is vital to health, safety, security, and improved quality of life. GE Vernova is headquartered in Cambridge, Massachusetts, U.S., with approximately 85,000 employees across approximately 100 countries around the world. Supported by the Company's purpose, The Energy to Change the World, GE Vernova technology helps deliver a more affordable, reliable, sustainable, and secure energy future.
GE Vernova's Wind segment is focused on delivering a suite of wind products and services to help accelerate a new era of energy by harnessing the power of wind. Technologies provided to customers include the next generation high efficiency 3-megawatt onshore wind turbine and the Haliade-X offshore wind turbine platform, as well as maintenance solutions and life extension optionality.
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Forward-Looking Statements
This document contains forward-looking statements - that is, statements related to future events that by their nature address matters that are, to different degrees, uncertain. These forward-looking statements often address GE Vernova's expected future business and financial performance and financial condition, and the expected performance of its products, the impact of its services and the results they may generate or produce, and often contain words such as "expect," "anticipate," "intend," "plan," "believe," "seek," "see," "will," "would," "estimate," "forecast," "target," "preliminary," or "range." Forward-looking statements by their nature address matters that are, to different degrees, uncertain, such as statements about planned and potential transactions, investments or projects and their expected results and the impacts of macroeconomic and market conditions and volatility on the Company's business operations, financial results and financial position and on the global supply chain and world economy.
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Notes to editor:
*/ The order was booked in the second quarter of 2026.
**/ GE Vernova's 4.2MW turbine with a 117-meter rotor is referred to as the 4.2MW-117m.
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Original text here: https://www.gevernova.com/news/press-releases/ge-vernova-supply-294-mw-wind-capacity-eurus-energys-hiyamizutouge-project-japan
[Category: BizEnergy]
AstraZeneca: Enhertu Demonstrated a Median Progression-free Survival of 14.3 Months as 1st-line Therapy in Patients With HER2-mutant Advanced Non-small Cell Lung Cancer in DESTINY-Lung04 Phase III Trial
WILMINGTON, Delaware, Sept. 15 -- AstraZeneca, a biopharmaceutical company, issued the following news release:
* * *
ENHERTU(R) (fam-trastuzumab deruxtecan-nxki) demonstrated a median progression-free survival of 14.3 months as 1st-line therapy in patients with HER2-mutant advanced non-small cell lung cancer in DESTINY-Lung04 Phase III trial
6-month improvement in median progression-free survival vs. pembrolizumab plus chemotherapy
AstraZeneca and Daiichi Sankyo's ENHERTU is the first HER2-directed therapy to
delay disease progression over standard of care in a Phase III trial in this setting
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Positive ... Show Full Article WILMINGTON, Delaware, Sept. 15 -- AstraZeneca, a biopharmaceutical company, issued the following news release: * * * ENHERTU(R) (fam-trastuzumab deruxtecan-nxki) demonstrated a median progression-free survival of 14.3 months as 1st-line therapy in patients with HER2-mutant advanced non-small cell lung cancer in DESTINY-Lung04 Phase III trial 6-month improvement in median progression-free survival vs. pembrolizumab plus chemotherapy AstraZeneca and Daiichi Sankyo's ENHERTU is the first HER2-directed therapy to delay disease progression over standard of care in a Phase III trial in this setting - Positiveresults from the DESTINY-Lung04 Phase III trial showed AstraZeneca and Daiichi Sankyo's ENHERTU(R) (fam-trastuzumab deruxtecan-nxki) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as a 1st-line treatment of patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer (NSCLC).
Results were presented today during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer (#WCLC26) hosted by the International Association for the Study of Lung Cancer in Seoul, South Korea (abstract #PL03.08).
In the primary endpoint of PFS, ENHERTU monotherapy significantly reduced the risk of disease progression or death by 37.0% versus pembrolizumab plus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.50-0.79; p<0.0001). Median PFS was 14.3 months with ENHERTU compared to 8.3 months for pembrolizumab plus chemotherapy as assessed by blinded independent central review (BICR). A favorable PFS trend was seen for ENHERTU across key subgroups, including the prespecified stratification factors of brain metastases, liver metastases, smoking status, HER2 mutation status (exon 19 or exon 20), and de novo or recurrent disease.
Objective response rate (ORR) with ENHERTU was 70.0% versus 44.5% with pembrolizumab plus chemotherapy. Median duration of response (DoR) for ENHERTU was 13.4 months and 9.7 months with pembrolizumab plus chemotherapy.
Julia Rotow, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute and lead investigator of the trial, said: "HER2-mutant non-small cell lung cancer is an aggressive disease with limited responses to current 1st-line standard of care, and many patients experience disease progression within a year of starting treatment. With seventy percent of patients responding and a median progression-free survival of 14.3 months, trastuzumab deruxtecan has the potential to become an important new 1st-line treatment option for these patients."
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "DESTINY-Lung04 is the first Phase III trial to demonstrate superior progression-free survival versus the global 1st-line standard of care in patients with HER2-mutant advanced non-small cell lung cancer. These results add to the growing body of evidence supporting ENHERTU as an important treatment for patients with HER2 alterations and underscore its potential role at the time of metastatic diagnosis, when treatment has the greatest opportunity to improve outcomes."
John Tsai, Global Head, R&D, Daiichi Sankyo, said: "ENHERTU was the first HER2-directed medicine and antibody drug conjugate approved for patients with HER2-mutant non-small cell lung cancer and has become a second-line standard-of-care treatment. The progression-free survival benefit of six months and strong response rates seen in DESTINY-Lung04 reinforce the importance of targeting HER2 directly in these patients and support the potential of ENHERTU in the 1st-line setting where delaying disease progression for as long as possible is a critical goal."
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TABLE: Summary of results: DESTINY-Lung04i
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At the time of analysis, the overall survival (OS) data were 46.9% mature and no formal hypothesis testing was performed. While there was no observed benefit in OS, varied and imbalanced subsequent therapy patterns between arms may limit the interpretation of this result. Imbalances include greater use of HER2-directed therapies in the pembrolizumab plus chemotherapy arm versus the ENHERTU arm (48.0% vs 23.3%) and limited use of subsequent immunotherapy plus chemotherapy in the ENHERTU arm (23.8%).
The safety profile of ENHERTU observed in DESTINY-Lung04 was generally consistent with its known profile with no new safety concerns identified.
Despite longer treatment exposure in the ENHERTU arm (median 12.3 months versus 7.1 months), Grade 3 or higher treatment related adverse events (AEs) were comparable between ENHERTU and pembrolizumab plus chemotherapy (34.1% in the ENHERTU arm and 33.6% in the pembrolizumab plus chemotherapy arm). The most common Grade 3 or higher AE occurring in 5% or more of patients treated in both arms was neutropenia (occurring in 11.1% of patients in the ENHERTU arm and 14.1% in the pembrolizumab plus chemotherapy arm). Interstitial lung disease (ILD) or pneumonitis events occurred in 20.8% of patients treated with ENHERTU as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low Grade (Grade 1 [n=7; 3.1%] or Grade 2 [n=30; 13.3%]). There were five Grade 3 (2.2%), one Grade 4 (0.4%) and four Grade 5 (1.8%) ILD events in the ENHERTU arm.
ENHERTU is approved to treat patients with previously treated metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and to treat patients with HER2-positive solid tumors, including HER2-overexpressing metastatic NSCLC, who have received prior treatment and who have no satisfactory treatment options.
ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
Enhertu U.S. Indications and Important Safety Information
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for:
* HER2-Positive Early Breast Cancer
- As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP)
- As adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment
* HER2-Positive Metastatic Breast Cancer
- In combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or, in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
* HER2-Low and HER2-Ultralow Metastatic Breast Cancer
- As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine therapies in the metastatic setting
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy
* HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC)
- As monotherapy for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-authorized test, and who have received a prior systemic therapy
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
* HER2-Positive Locally Advanced or Metastatic Gastric Cancer
- As monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen
* HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
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TABLE: Important Safety Information
* * *
Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in 28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., 0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., 1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. In the adjuvant HER2+ breast cancer setting, if drug-induced ILD is suspected, rule out radiotherapy-related pneumonitis. If only radiotherapy-related pneumonitis is suspected, consider interruption of ENHERTU for Grade 2 and permanently discontinue ENHERTU for Grade 3.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), ILD occurred in 12% of patients. Median time to first onset was 8.0 months (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.5% of patients treated with ENHERTU in combination with pertuzumab.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, ILD occurred in 4.4% of patients. Median time to first onset was 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or pneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3- C or a sustained temperature of 38- C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), decreased neutrophil count occurred in 79% of patients. Median time to first onset was 22 days (range: 5 to 994). Twenty-nine percent had Grade 3 or 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of patients.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, a decrease in neutrophil count was reported in 58% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 42 days (range: 11 to 165). Febrile neutropenia was reported in 0.9% of patients.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular dysfunction (LVD) has been observed with anti-HER2 therapies, including ENHERTU. Assess left ventricular ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVD through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, LVD was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), LVEF decrease was reported in 11% of patients, of which 2.1% were Grade 3 or 4.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, LVD was reported in 1.3% of patients, of which 0.3% were Grade 3.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.
Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level.
Adverse Reactions
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for >6 months and 39% were exposed for >1 year. In this pooled safety population, the most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (43%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%).
ENHERTU in Combination with Pertuzumab
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg in combination with pertuzumab intravenously every 3 weeks in 431 patients in DESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381). Among these patients, 86% were exposed for >6 months and 73% were exposed for >1 year. In this pooled safety population, the most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased hemoglobin (80%), decreased neutrophil count (79%), nausea (74%), increased alanine aminotransferase (65%), diarrhea (64%), increased aspartate aminotransferase (63%), decreased lymphocyte count (61%), decreased platelet count (55%), increased blood alkaline phosphatase (54%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (32%), constipation (31%), decreased appetite (31%), decreased weight (28%), musculoskeletal pain (23%), increased blood bilirubin (23%), and abdominal pain (22%).
HER2-Positive Early Breast Cancer
DESTINY-Breast11
The safety of ENHERTU followed by THP was evaluated in 320 patients with HER2-positive (IHC 3+ or ISH+) early breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11. ENHERTU was administered by intravenous infusion once every three weeks for 4 cycles followed by THP for 4 cycles. The median duration of treatment was 5.6 months (range: 0.7 to 9.1) for patients who received ENHERTU followed by THP.
Serious adverse reactions occurred in 11% of patients receiving ENHERTU followed by THP, including COVID-19 (0.9%) and ILD/pneumonitis (0.6%). Fatal adverse reactions occurred in 0.6% of patients, including ILD/pneumonitis and death not otherwise specified (1 patient each).
In patients treated with ENHERTU followed by THP, the permanent discontinuation of ENHERTU due to adverse reactions occurred in 1.3%, of which ILD/pneumonitis accounted for 0.6%. Dose interruptions of ENHERTU due to adverse reactions occurred in 11% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count and COVID-19. Dose reductions of ENHERTU occurred in 2.5% of patients treated with ENHERTU.
The most common (20%) adverse reactions in patients treated with ENHERTU followed by THP, including laboratory abnormalities, were decreased hemoglobin (83%), increased alanine aminotransferase (79%), increased aspartate aminotransferase (74%), decreased white blood cell count (67%), nausea (65%), peripheral neuropathy (59%), diarrhea (59%), decreased neutrophil count (58%), alopecia (48%), fatigue (41%), decreased lymphocyte count (40%), rash (31%), musculoskeletal pain (30%), decreased blood potassium (29%), constipation (29%), vomiting (29%), stomatitis (23%), and decreased appetite (20%).
DESTINY-Breast05
The safety of ENHERTU was evaluated in 806 patients with HER2-positive breast cancer with residual invasive disease following neoadjuvant HER2-targeted therapy who then received at least one dose of ENHERTU 5.4 mg/kg. ENHERTU was administered by intravenous infusion once every three weeks for 14 cycles. The median duration of treatment was 10 months (range: 0.7 to 16) for patients who received ENHERTU.
Serious adverse reactions occurred in 17% of patients receiving ENHERTU. Serious adverse reactions in 1% of patients who received ENHERTU were ILD/pneumonitis, radiation pneumonitis, pneumonia, and platelet count decreased. Fatal adverse reactions occurred in 0.4% of patients including ILD/pneumonitis (2 patients) and respiratory tract infection (1 patient).
Permanent discontinuation of ENHERTU due to an adverse reaction occurred in 18% of patients. The adverse reaction which resulted in permanent discontinuation of ENHERTU >2% included ILD/pneumonitis. Dose interruptions of ENHERTU due to an adverse reaction occurred in 50% of patients. Adverse reactions which required dosage interruptions in >2% included radiation pneumonitis, neutrophil count decreased, COVID-19, white blood cell count decreased, ILD/pneumonitis, platelet count decreased, upper respiratory tract infection, fatigue, cough, and pyrexia. Dose reductions of ENHERTU due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reductions in >2% of patients included nausea, fatigue, platelet count decreased, ILD/pneumonitis, and neutrophil count decreased.
The most common (20%) adverse reactions, including laboratory abnormalities, in patients receiving ENHERTU were decreased white blood cell count (80%), decreased lymphocyte count (72%), decreased neutrophil count (72%), nausea (71%), decreased hemoglobin (61%), increased aspartate aminotransferase (60%), fatigue (54%), increased alanine aminotransferase (53%), decreased platelet count (46%), increased blood alkaline phosphatase (39%), constipation (32%), vomiting (31%), decreased blood potassium (27%), diarrhea (23%), musculoskeletal pain (23%), and decreased appetite (20%).
ILD was reported in 17% of patients receiving ENHERTU, which included COVID-19 pneumonia, interstitial lung disease, lung opacity, organizing pneumonia, pneumocystis jirovecii pneumonia, pneumonia, and pneumonitis which was adjudicated as ILD (irrespective of causality). Adjudicated drug-related ILD for ENHERTU was 10% for all Grades and 0.9% for Grades 3 or 4.
HER2-Positive Metastatic Breast Cancer
DESTINY-Breast09
The safety of ENHERTU 5.4 mg/kg in combination with pertuzumab was evaluated in DESTINY-Breast09, a randomized, three-arm, multicenter study including 763 patients with HER2-positive (IHC 3+ or ISH+) unresectable or metastatic breast cancer. Three hundred eighty-one patients received ENHERTU in combination with pertuzumab and 382 patients received THP (taxane [docetaxel or paclitaxel], trastuzumab, and pertuzumab). Among patients who received ENHERTU in combination with pertuzumab, the median duration of treatment was 22 months (range: 0.3 months to 44.5 months).
Serious adverse reactions occurred in 27% of patients receiving ENHERTU in combination with pertuzumab. Serious adverse reactions in >1% of patients were diarrhea, pneumonia, febrile neutropenia, hypokalemia, vomiting, ILD, pulmonary embolism, and sepsis. Fatalities due to adverse reactions occurred in 3.4% of patients including pneumonia (n=3), ILD (n=2), sepsis (n=2), pulmonary embolism, septic shock, acute kidney injury, dyspnea, febrile neutropenia, and intestinal ischemia (1 patient each).
ENHERTU was discontinued for adverse reactions in 21% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis (6%). Dose interruptions due to adverse reactions occurred in 69% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, neutropenia, upper respiratory tract infection, fatigue, anemia, hypokalemia, ILD/pneumonitis, thrombocytopenia, pneumonia, diarrhea, transaminase increased, leukopenia, cough, pyrexia, decreased appetite, and blood bilirubin increased. Dose reductions occurred in 46% of patients treated with ENHERTU in combination with pertuzumab. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, neutropenia, nausea, diarrhea, ILD/pneumonitis, thrombocytopenia, vomiting, transaminases increased, decreased weight, febrile neutropenia, and hypokalemia.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (87%), decreased hemoglobin (80%), decreased neutrophil count (78%), nausea (75%), increased alanine aminotransferase (66%), diarrhea (64%), increased aspartate aminotransferase (62%), decreased lymphocyte count (62%), decreased platelet count (56%), increased blood alkaline phosphatase (55%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (33%), constipation (33%), decreased appetite (32%), decreased weight (30%), COVID-19 (28%), musculoskeletal pain (24%), increased blood bilirubin (23%), and abdominal pain (23%).
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received ENHERTU.
Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (1 patient each).
ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue.
The most common (20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%).
HER2-Low and HER2-Ultralow Metastatic Breast Cancer
DESTINY-Breast06
The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast06. The median duration of treatment was 11 months (range: 0.4 to 39.6) for patients who received ENHERTU.
Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities due to adverse reactions occurred in 2.8% of patients including ILD (0.7%); sepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis, neutropenic sepsis, peritonitis, cerebrovascular accident, general physical health deterioration (0.2% each).
ENHERTU was permanently discontinued in 14% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, decreased neutrophil count, anemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose reductions occurred in 25% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, fatigue, decreased platelet count, and decreased neutrophil count.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased neutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased lymphocyte count (66%), fatigue (53%), decreased platelet count (48%), alopecia (48%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (43%), increased aspartate aminotransferase (41%), decreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation (32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain (24%).
DESTINY-Breast04
The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.
Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each).
ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia.
The most common (20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%).
HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)
DESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.
The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity in DESTINY Lung02. The median duration of treatment was 8 months (range: 0.7 to 28) for patients who received ENHERTU.
Serious adverse reactions occurred in 40% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pleural effusion, thrombocytopenia, dyspnea, nausea, pneumonia, vomiting, myocarditis, pulmonary embolism, and increased troponin I. Fatalities due to adverse reactions occurred in 3% of patients including ILD/pneumonitis, cerebrovascular accident, and pneumococcal sepsis (1 patient each).
ENHERTU was permanently discontinued in 17% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, pneumonia, blood bilirubin increased, hypokalemia, metastases to meninges, and myocarditis. Dose interruptions of ENHERTU due to adverse reactions occurred in 50% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia, COVID-19, ILD/pneumonitis, fatigue, anemia, and pneumonia. Dose reductions due to an adverse reaction occurred in 20% of patients. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, fatigue, and decreased appetite.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (68%), nausea (67%), decreased white blood cell count (66%), decreased neutrophil count (59%), decreased lymphocyte count (56%), increased aspartate aminotransferase (51%), decreased albumin (50%), decreased platelet count (49%), fatigue (48%), increased alanine aminotransferase (41%), decreased appetite (41%), constipation (38%), increased alkaline phosphatase (37%), vomiting (32%), decreased blood potassium (29%), diarrhea (24%), alopecia (22%), and musculoskeletal pain (21%).
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU.
Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in 1 patient each (0.8%).
ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood potassium. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%).
HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2).
Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1 patient each (0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and hemorrhagic shock.
ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose reductions occurred in 27% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%), decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%).
Use in Specific Populations
* Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU.
* Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
* Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
* Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
* Geriatric Use: ENHERTU as Monotherapy: Of the 2233 patients treated with ENHERTU 5.4 mg/kg, 28% were 65 years and 6% were 75 years. No overall differences in efficacy within clinical studies were observed between patients 65 years compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged 65 years (56%) as compared to younger patients (49%). Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were 65 years and 14% were 75 years. No overall differences in efficacy or safety were observed between patients 65 years of age compared to younger patients. ENHERTU in Combination with Pertuzumab: In patients with HER2-positive unresectable or metastatic breast cancer treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), 17% were 65 years and 3% were 75 years. No overall differences in efficacy or safety were observed between patients 65 years compared to younger patients. ENHERTU followed by THP: Of the 320 patients with HER2-positive early breast cancer treated with ENHERTU 5.4 mg/kg followed by THP, 12% were 65 years and 1.6% were 75 years. No overall differences in efficacy were observed between patients 65 years compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients 65 years (38%) as compared to younger patients (30%).
* Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min).
* Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, monitor for increased adverse reactions related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).
ting
Positive results from the DESTINY-Lung04 Phase III trial showed AstraZeneca and Daiichi Sankyo's ENHERTU(R) (fam-trastuzumab deruxtecan-nxki) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as a 1st-line treatment of patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer (NSCLC).
Results were presented today during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer (#WCLC26) hosted by the International Association for the Study of Lung Cancer in Seoul, South Korea (abstract #PL03.08).
In the primary endpoint of PFS, ENHERTU monotherapy significantly reduced the risk of disease progression or death by 37.0% versus pembrolizumab plus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.50-0.79; p<0.0001). Median PFS was 14.3 months with ENHERTU compared to 8.3 months for pembrolizumab plus chemotherapy as assessed by blinded independent central review (BICR). A favorable PFS trend was seen for ENHERTU across key subgroups, including the prespecified stratification factors of brain metastases, liver metastases, smoking status, HER2 mutation status (exon 19 or exon 20), and de novo or recurrent disease.
Objective response rate (ORR) with ENHERTU was 70.0% versus 44.5% with pembrolizumab plus chemotherapy. Median duration of response (DoR) for ENHERTU was 13.4 months and 9.7 months with pembrolizumab plus chemotherapy.
Julia Rotow, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute and lead investigator of the trial, said: "HER2-mutant non-small cell lung cancer is an aggressive disease with limited responses to current 1st-line standard of care, and many patients experience disease progression within a year of starting treatment. With seventy percent of patients responding and a median progression-free survival of 14.3 months, trastuzumab deruxtecan has the potential to become an important new 1st-line treatment option for these patients."
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "DESTINY-Lung04 is the first Phase III trial to demonstrate superior progression-free survival versus the global 1st-line standard of care in patients with HER2-mutant advanced non-small cell lung cancer. These results add to the growing body of evidence supporting ENHERTU as an important treatment for patients with HER2 alterations and underscore its potential role at the time of metastatic diagnosis, when treatment has the greatest opportunity to improve outcomes."
John Tsai, Global Head, R&D, Daiichi Sankyo, said: "ENHERTU was the first HER2-directed medicine and antibody drug conjugate approved for patients with HER2-mutant non-small cell lung cancer and has become a second-line standard-of-care treatment. The progression-free survival benefit of six months and strong response rates seen in DESTINY-Lung04 reinforce the importance of targeting HER2 directly in these patients and support the potential of ENHERTU in the 1st-line setting where delaying disease progression for as long as possible is a critical goal."
Summary of results: DESTINY-Lung04i
Efficacy measure ENHERTU
(5.4mg/kg; n=227) Pembrolizumab plus
chemotherapy
(n=227)
PFSii
Median PFS, (months) (95% CI) 14.3
(12.4-16.5) 8.3
(7.0-9.9)
Hazard ratio (95% CI) HR 0.63 (0.50-0.79)
p-value p<0.0001
ORRii,iii
ORR(%) (n)
(95% CI)iv 70.0% (159)
(63.6-75.9) 44.5% (101)
(37.9-51.2)
CR, % (n) 1.8% (4) 1.8% (4)
PR, % (n) 68.3% (155) 42.7% (97)
Median DOR, (months) (95% CI) 13.4
(10.4-17.2) 9.7
(7.0-11.1)
PFS2iii,v
Median PFS2, (months) (95% CI) 22.7
(20.3-26.3) 17.3
(15.6-21.8)
Hazard ratio (95% CI) HR 0.80 (0.62-1.02)
OSvi
Median OS, (months) (95% CI) 29.3
(26.2-33.4) 33.1
(27.7-40.7)
Hazard ratio (95% CI) HR 1.15 (0.88-1.52)
CI, confidence interval; CR, complete response; DOR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response
i Analysis was based on a data cut-off (DCO) of 9 June 2026; median duration of follow-up was 21.6 in the ENHERTU arm and 20.4 months in the pembrolizumab plus chemotherapy arm. At DCO, 40 patients (17.7%) remained in the ENHERTU arm and 10 patients (4.5%) in the pembrolizumab plus chemotherapy arm.
ii Assessed by BICR
iii Assessed by investigator
iv ORR is (CR + PR); includes unconfirmed responses
v PFS2 is defined as the time from randomization to second progression (earliest progression event following first subsequent therapy) or death
vi At DCO, overall data maturity for OS was 46.9% and no formal hypothesis testing was performed; formal hypothesis testing will be performed at the second interim analysis and final analysis
At the time of analysis, the overall survival (OS) data were 46.9% mature and no formal hypothesis testing was performed. While there was no observed benefit in OS, varied and imbalanced subsequent therapy patterns between arms may limit the interpretation of this result. Imbalances include greater use of HER2-directed therapies in the pembrolizumab plus chemotherapy arm versus the ENHERTU arm (48.0% vs 23.3%) and limited use of subsequent immunotherapy plus chemotherapy in the ENHERTU arm (23.8%).
The safety profile of ENHERTU observed in DESTINY-Lung04 was generally consistent with its known profile with no new safety concerns identified.
Despite longer treatment exposure in the ENHERTU arm (median 12.3 months versus 7.1 months), Grade 3 or higher treatment related adverse events (AEs) were comparable between ENHERTU and pembrolizumab plus chemotherapy (34.1% in the ENHERTU arm and 33.6% in the pembrolizumab plus chemotherapy arm). The most common Grade 3 or higher AE occurring in 5% or more of patients treated in both arms was neutropenia (occurring in 11.1% of patients in the ENHERTU arm and 14.1% in the pembrolizumab plus chemotherapy arm). Interstitial lung disease (ILD) or pneumonitis events occurred in 20.8% of patients treated with ENHERTU as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low Grade (Grade 1 [n=7; 3.1%] or Grade 2 [n=30; 13.3%]). There were five Grade 3 (2.2%), one Grade 4 (0.4%) and four Grade 5 (1.8%) ILD events in the ENHERTU arm.
ENHERTU is approved to treat patients with previously treated metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and to treat patients with HER2-positive solid tumors, including HER2-overexpressing metastatic NSCLC, who have received prior treatment and who have no satisfactory treatment options.
ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
Enhertu U.S. Indications and Important Safety Information
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for:
HER2-Positive Early Breast Cancer
- As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP)
- As adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment
HER2-Positive Metastatic Breast Cancer
- In combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or, in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
HER2-Low and HER2-Ultralow Metastatic Breast Cancer
- As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine therapies in the metastatic setting
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy
HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC)
- As monotherapy for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-authorized test, and who have received a prior systemic therapy
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer
- As monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen
HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Important Safety Information
ETCAMAH
Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in 28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., 0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., 1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. In the adjuvant HER2+ breast cancer setting, if drug-induced ILD is suspected, rule out radiotherapy-related pneumonitis. If only radiotherapy-related pneumonitis is suspected, consider interruption of ENHERTU for Grade 2 and permanently discontinue ENHERTU for Grade 3.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), ILD occurred in 12% of patients. Median time to first onset was 8.0 months (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.5% of patients treated with ENHERTU in combination with pertuzumab.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, ILD occurred in 4.4% of patients. Median time to first onset was 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or pneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3- C or a sustained temperature of 38- C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), decreased neutrophil count occurred in 79% of patients. Median time to first onset was 22 days (range: 5 to 994). Twenty-nine percent had Grade 3 or 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of patients.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, a decrease in neutrophil count was reported in 58% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 42 days (range: 11 to 165). Febrile neutropenia was reported in 0.9% of patients.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular dysfunction (LVD) has been observed with anti-HER2 therapies, including ENHERTU. Assess left ventricular ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVD through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, LVD was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), LVEF decrease was reported in 11% of patients, of which 2.1% were Grade 3 or 4.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, LVD was reported in 1.3% of patients, of which 0.3% were Grade 3.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.
Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level.
Adverse Reactions
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for >6 months and 39% were exposed for >1 year. In this pooled safety population, the most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (43%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%).
ENHERTU in Combination with Pertuzumab
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg in combination with pertuzumab intravenously every 3 weeks in 431 patients in DESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381). Among these patients, 86% were exposed for >6 months and 73% were exposed for >1 year. In this pooled safety population, the most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased hemoglobin (80%), decreased neutrophil count (79%), nausea (74%), increased alanine aminotransferase (65%), diarrhea (64%), increased aspartate aminotransferase (63%), decreased lymphocyte count (61%), decreased platelet count (55%), increased blood alkaline phosphatase (54%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (32%), constipation (31%), decreased appetite (31%), decreased weight (28%), musculoskeletal pain (23%), increased blood bilirubin (23%), and abdominal pain (22%).
HER2-Positive Early Breast Cancer
DESTINY-Breast11
The safety of ENHERTU followed by THP was evaluated in 320 patients with HER2-positive (IHC 3+ or ISH+) early breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11. ENHERTU was administered by intravenous infusion once every three weeks for 4 cycles followed by THP for 4 cycles. The median duration of treatment was 5.6 months (range: 0.7 to 9.1) for patients who recei
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ENHERTU(R) (fam-trastuzumab deruxtecan-nxki) demonstrated a median progression-free survival of 14.3 months as 1st-line therapy in patients with HER2-mutant advanced non-small cell lung cancer in DESTINY-Lung04 Phase III trial
6-month improvement in median progression-free survival vs. pembrolizumab plus chemotherapy
AstraZeneca and Daiichi Sankyo's ENHERTU is the first HER2-directed therapy to
delay disease progression over standard of care in a Phase III trial in this setting
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Positive ... Show Full Article WILMINGTON, Delaware, Sept. 15 -- AstraZeneca, a biopharmaceutical company, issued the following news release: * * * ENHERTU(R) (fam-trastuzumab deruxtecan-nxki) demonstrated a median progression-free survival of 14.3 months as 1st-line therapy in patients with HER2-mutant advanced non-small cell lung cancer in DESTINY-Lung04 Phase III trial 6-month improvement in median progression-free survival vs. pembrolizumab plus chemotherapy AstraZeneca and Daiichi Sankyo's ENHERTU is the first HER2-directed therapy to delay disease progression over standard of care in a Phase III trial in this setting - Positiveresults from the DESTINY-Lung04 Phase III trial showed AstraZeneca and Daiichi Sankyo's ENHERTU(R) (fam-trastuzumab deruxtecan-nxki) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as a 1st-line treatment of patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer (NSCLC).
Results were presented today during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer (#WCLC26) hosted by the International Association for the Study of Lung Cancer in Seoul, South Korea (abstract #PL03.08).
In the primary endpoint of PFS, ENHERTU monotherapy significantly reduced the risk of disease progression or death by 37.0% versus pembrolizumab plus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.50-0.79; p<0.0001). Median PFS was 14.3 months with ENHERTU compared to 8.3 months for pembrolizumab plus chemotherapy as assessed by blinded independent central review (BICR). A favorable PFS trend was seen for ENHERTU across key subgroups, including the prespecified stratification factors of brain metastases, liver metastases, smoking status, HER2 mutation status (exon 19 or exon 20), and de novo or recurrent disease.
Objective response rate (ORR) with ENHERTU was 70.0% versus 44.5% with pembrolizumab plus chemotherapy. Median duration of response (DoR) for ENHERTU was 13.4 months and 9.7 months with pembrolizumab plus chemotherapy.
Julia Rotow, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute and lead investigator of the trial, said: "HER2-mutant non-small cell lung cancer is an aggressive disease with limited responses to current 1st-line standard of care, and many patients experience disease progression within a year of starting treatment. With seventy percent of patients responding and a median progression-free survival of 14.3 months, trastuzumab deruxtecan has the potential to become an important new 1st-line treatment option for these patients."
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "DESTINY-Lung04 is the first Phase III trial to demonstrate superior progression-free survival versus the global 1st-line standard of care in patients with HER2-mutant advanced non-small cell lung cancer. These results add to the growing body of evidence supporting ENHERTU as an important treatment for patients with HER2 alterations and underscore its potential role at the time of metastatic diagnosis, when treatment has the greatest opportunity to improve outcomes."
John Tsai, Global Head, R&D, Daiichi Sankyo, said: "ENHERTU was the first HER2-directed medicine and antibody drug conjugate approved for patients with HER2-mutant non-small cell lung cancer and has become a second-line standard-of-care treatment. The progression-free survival benefit of six months and strong response rates seen in DESTINY-Lung04 reinforce the importance of targeting HER2 directly in these patients and support the potential of ENHERTU in the 1st-line setting where delaying disease progression for as long as possible is a critical goal."
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TABLE: Summary of results: DESTINY-Lung04i
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At the time of analysis, the overall survival (OS) data were 46.9% mature and no formal hypothesis testing was performed. While there was no observed benefit in OS, varied and imbalanced subsequent therapy patterns between arms may limit the interpretation of this result. Imbalances include greater use of HER2-directed therapies in the pembrolizumab plus chemotherapy arm versus the ENHERTU arm (48.0% vs 23.3%) and limited use of subsequent immunotherapy plus chemotherapy in the ENHERTU arm (23.8%).
The safety profile of ENHERTU observed in DESTINY-Lung04 was generally consistent with its known profile with no new safety concerns identified.
Despite longer treatment exposure in the ENHERTU arm (median 12.3 months versus 7.1 months), Grade 3 or higher treatment related adverse events (AEs) were comparable between ENHERTU and pembrolizumab plus chemotherapy (34.1% in the ENHERTU arm and 33.6% in the pembrolizumab plus chemotherapy arm). The most common Grade 3 or higher AE occurring in 5% or more of patients treated in both arms was neutropenia (occurring in 11.1% of patients in the ENHERTU arm and 14.1% in the pembrolizumab plus chemotherapy arm). Interstitial lung disease (ILD) or pneumonitis events occurred in 20.8% of patients treated with ENHERTU as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low Grade (Grade 1 [n=7; 3.1%] or Grade 2 [n=30; 13.3%]). There were five Grade 3 (2.2%), one Grade 4 (0.4%) and four Grade 5 (1.8%) ILD events in the ENHERTU arm.
ENHERTU is approved to treat patients with previously treated metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and to treat patients with HER2-positive solid tumors, including HER2-overexpressing metastatic NSCLC, who have received prior treatment and who have no satisfactory treatment options.
ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
Enhertu U.S. Indications and Important Safety Information
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for:
* HER2-Positive Early Breast Cancer
- As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP)
- As adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment
* HER2-Positive Metastatic Breast Cancer
- In combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or, in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
* HER2-Low and HER2-Ultralow Metastatic Breast Cancer
- As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine therapies in the metastatic setting
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy
* HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC)
- As monotherapy for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-authorized test, and who have received a prior systemic therapy
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
* HER2-Positive Locally Advanced or Metastatic Gastric Cancer
- As monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen
* HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
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TABLE: Important Safety Information
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Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in 28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., 0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., 1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. In the adjuvant HER2+ breast cancer setting, if drug-induced ILD is suspected, rule out radiotherapy-related pneumonitis. If only radiotherapy-related pneumonitis is suspected, consider interruption of ENHERTU for Grade 2 and permanently discontinue ENHERTU for Grade 3.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), ILD occurred in 12% of patients. Median time to first onset was 8.0 months (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.5% of patients treated with ENHERTU in combination with pertuzumab.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, ILD occurred in 4.4% of patients. Median time to first onset was 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or pneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3- C or a sustained temperature of 38- C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), decreased neutrophil count occurred in 79% of patients. Median time to first onset was 22 days (range: 5 to 994). Twenty-nine percent had Grade 3 or 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of patients.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, a decrease in neutrophil count was reported in 58% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 42 days (range: 11 to 165). Febrile neutropenia was reported in 0.9% of patients.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular dysfunction (LVD) has been observed with anti-HER2 therapies, including ENHERTU. Assess left ventricular ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVD through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, LVD was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), LVEF decrease was reported in 11% of patients, of which 2.1% were Grade 3 or 4.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, LVD was reported in 1.3% of patients, of which 0.3% were Grade 3.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.
Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level.
Adverse Reactions
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for >6 months and 39% were exposed for >1 year. In this pooled safety population, the most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (43%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%).
ENHERTU in Combination with Pertuzumab
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg in combination with pertuzumab intravenously every 3 weeks in 431 patients in DESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381). Among these patients, 86% were exposed for >6 months and 73% were exposed for >1 year. In this pooled safety population, the most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased hemoglobin (80%), decreased neutrophil count (79%), nausea (74%), increased alanine aminotransferase (65%), diarrhea (64%), increased aspartate aminotransferase (63%), decreased lymphocyte count (61%), decreased platelet count (55%), increased blood alkaline phosphatase (54%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (32%), constipation (31%), decreased appetite (31%), decreased weight (28%), musculoskeletal pain (23%), increased blood bilirubin (23%), and abdominal pain (22%).
HER2-Positive Early Breast Cancer
DESTINY-Breast11
The safety of ENHERTU followed by THP was evaluated in 320 patients with HER2-positive (IHC 3+ or ISH+) early breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11. ENHERTU was administered by intravenous infusion once every three weeks for 4 cycles followed by THP for 4 cycles. The median duration of treatment was 5.6 months (range: 0.7 to 9.1) for patients who received ENHERTU followed by THP.
Serious adverse reactions occurred in 11% of patients receiving ENHERTU followed by THP, including COVID-19 (0.9%) and ILD/pneumonitis (0.6%). Fatal adverse reactions occurred in 0.6% of patients, including ILD/pneumonitis and death not otherwise specified (1 patient each).
In patients treated with ENHERTU followed by THP, the permanent discontinuation of ENHERTU due to adverse reactions occurred in 1.3%, of which ILD/pneumonitis accounted for 0.6%. Dose interruptions of ENHERTU due to adverse reactions occurred in 11% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count and COVID-19. Dose reductions of ENHERTU occurred in 2.5% of patients treated with ENHERTU.
The most common (20%) adverse reactions in patients treated with ENHERTU followed by THP, including laboratory abnormalities, were decreased hemoglobin (83%), increased alanine aminotransferase (79%), increased aspartate aminotransferase (74%), decreased white blood cell count (67%), nausea (65%), peripheral neuropathy (59%), diarrhea (59%), decreased neutrophil count (58%), alopecia (48%), fatigue (41%), decreased lymphocyte count (40%), rash (31%), musculoskeletal pain (30%), decreased blood potassium (29%), constipation (29%), vomiting (29%), stomatitis (23%), and decreased appetite (20%).
DESTINY-Breast05
The safety of ENHERTU was evaluated in 806 patients with HER2-positive breast cancer with residual invasive disease following neoadjuvant HER2-targeted therapy who then received at least one dose of ENHERTU 5.4 mg/kg. ENHERTU was administered by intravenous infusion once every three weeks for 14 cycles. The median duration of treatment was 10 months (range: 0.7 to 16) for patients who received ENHERTU.
Serious adverse reactions occurred in 17% of patients receiving ENHERTU. Serious adverse reactions in 1% of patients who received ENHERTU were ILD/pneumonitis, radiation pneumonitis, pneumonia, and platelet count decreased. Fatal adverse reactions occurred in 0.4% of patients including ILD/pneumonitis (2 patients) and respiratory tract infection (1 patient).
Permanent discontinuation of ENHERTU due to an adverse reaction occurred in 18% of patients. The adverse reaction which resulted in permanent discontinuation of ENHERTU >2% included ILD/pneumonitis. Dose interruptions of ENHERTU due to an adverse reaction occurred in 50% of patients. Adverse reactions which required dosage interruptions in >2% included radiation pneumonitis, neutrophil count decreased, COVID-19, white blood cell count decreased, ILD/pneumonitis, platelet count decreased, upper respiratory tract infection, fatigue, cough, and pyrexia. Dose reductions of ENHERTU due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reductions in >2% of patients included nausea, fatigue, platelet count decreased, ILD/pneumonitis, and neutrophil count decreased.
The most common (20%) adverse reactions, including laboratory abnormalities, in patients receiving ENHERTU were decreased white blood cell count (80%), decreased lymphocyte count (72%), decreased neutrophil count (72%), nausea (71%), decreased hemoglobin (61%), increased aspartate aminotransferase (60%), fatigue (54%), increased alanine aminotransferase (53%), decreased platelet count (46%), increased blood alkaline phosphatase (39%), constipation (32%), vomiting (31%), decreased blood potassium (27%), diarrhea (23%), musculoskeletal pain (23%), and decreased appetite (20%).
ILD was reported in 17% of patients receiving ENHERTU, which included COVID-19 pneumonia, interstitial lung disease, lung opacity, organizing pneumonia, pneumocystis jirovecii pneumonia, pneumonia, and pneumonitis which was adjudicated as ILD (irrespective of causality). Adjudicated drug-related ILD for ENHERTU was 10% for all Grades and 0.9% for Grades 3 or 4.
HER2-Positive Metastatic Breast Cancer
DESTINY-Breast09
The safety of ENHERTU 5.4 mg/kg in combination with pertuzumab was evaluated in DESTINY-Breast09, a randomized, three-arm, multicenter study including 763 patients with HER2-positive (IHC 3+ or ISH+) unresectable or metastatic breast cancer. Three hundred eighty-one patients received ENHERTU in combination with pertuzumab and 382 patients received THP (taxane [docetaxel or paclitaxel], trastuzumab, and pertuzumab). Among patients who received ENHERTU in combination with pertuzumab, the median duration of treatment was 22 months (range: 0.3 months to 44.5 months).
Serious adverse reactions occurred in 27% of patients receiving ENHERTU in combination with pertuzumab. Serious adverse reactions in >1% of patients were diarrhea, pneumonia, febrile neutropenia, hypokalemia, vomiting, ILD, pulmonary embolism, and sepsis. Fatalities due to adverse reactions occurred in 3.4% of patients including pneumonia (n=3), ILD (n=2), sepsis (n=2), pulmonary embolism, septic shock, acute kidney injury, dyspnea, febrile neutropenia, and intestinal ischemia (1 patient each).
ENHERTU was discontinued for adverse reactions in 21% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis (6%). Dose interruptions due to adverse reactions occurred in 69% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, neutropenia, upper respiratory tract infection, fatigue, anemia, hypokalemia, ILD/pneumonitis, thrombocytopenia, pneumonia, diarrhea, transaminase increased, leukopenia, cough, pyrexia, decreased appetite, and blood bilirubin increased. Dose reductions occurred in 46% of patients treated with ENHERTU in combination with pertuzumab. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, neutropenia, nausea, diarrhea, ILD/pneumonitis, thrombocytopenia, vomiting, transaminases increased, decreased weight, febrile neutropenia, and hypokalemia.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (87%), decreased hemoglobin (80%), decreased neutrophil count (78%), nausea (75%), increased alanine aminotransferase (66%), diarrhea (64%), increased aspartate aminotransferase (62%), decreased lymphocyte count (62%), decreased platelet count (56%), increased blood alkaline phosphatase (55%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (33%), constipation (33%), decreased appetite (32%), decreased weight (30%), COVID-19 (28%), musculoskeletal pain (24%), increased blood bilirubin (23%), and abdominal pain (23%).
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received ENHERTU.
Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (1 patient each).
ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue.
The most common (20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%).
HER2-Low and HER2-Ultralow Metastatic Breast Cancer
DESTINY-Breast06
The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast06. The median duration of treatment was 11 months (range: 0.4 to 39.6) for patients who received ENHERTU.
Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities due to adverse reactions occurred in 2.8% of patients including ILD (0.7%); sepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis, neutropenic sepsis, peritonitis, cerebrovascular accident, general physical health deterioration (0.2% each).
ENHERTU was permanently discontinued in 14% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, decreased neutrophil count, anemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose reductions occurred in 25% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, fatigue, decreased platelet count, and decreased neutrophil count.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased neutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased lymphocyte count (66%), fatigue (53%), decreased platelet count (48%), alopecia (48%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (43%), increased aspartate aminotransferase (41%), decreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation (32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain (24%).
DESTINY-Breast04
The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.
Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each).
ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia.
The most common (20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%).
HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)
DESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.
The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity in DESTINY Lung02. The median duration of treatment was 8 months (range: 0.7 to 28) for patients who received ENHERTU.
Serious adverse reactions occurred in 40% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pleural effusion, thrombocytopenia, dyspnea, nausea, pneumonia, vomiting, myocarditis, pulmonary embolism, and increased troponin I. Fatalities due to adverse reactions occurred in 3% of patients including ILD/pneumonitis, cerebrovascular accident, and pneumococcal sepsis (1 patient each).
ENHERTU was permanently discontinued in 17% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, pneumonia, blood bilirubin increased, hypokalemia, metastases to meninges, and myocarditis. Dose interruptions of ENHERTU due to adverse reactions occurred in 50% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia, COVID-19, ILD/pneumonitis, fatigue, anemia, and pneumonia. Dose reductions due to an adverse reaction occurred in 20% of patients. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, fatigue, and decreased appetite.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (68%), nausea (67%), decreased white blood cell count (66%), decreased neutrophil count (59%), decreased lymphocyte count (56%), increased aspartate aminotransferase (51%), decreased albumin (50%), decreased platelet count (49%), fatigue (48%), increased alanine aminotransferase (41%), decreased appetite (41%), constipation (38%), increased alkaline phosphatase (37%), vomiting (32%), decreased blood potassium (29%), diarrhea (24%), alopecia (22%), and musculoskeletal pain (21%).
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU.
Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in 1 patient each (0.8%).
ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood potassium. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%).
HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2).
Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1 patient each (0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and hemorrhagic shock.
ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose reductions occurred in 27% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea.
The most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%), decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%).
Use in Specific Populations
* Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU.
* Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
* Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
* Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
* Geriatric Use: ENHERTU as Monotherapy: Of the 2233 patients treated with ENHERTU 5.4 mg/kg, 28% were 65 years and 6% were 75 years. No overall differences in efficacy within clinical studies were observed between patients 65 years compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged 65 years (56%) as compared to younger patients (49%). Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were 65 years and 14% were 75 years. No overall differences in efficacy or safety were observed between patients 65 years of age compared to younger patients. ENHERTU in Combination with Pertuzumab: In patients with HER2-positive unresectable or metastatic breast cancer treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), 17% were 65 years and 3% were 75 years. No overall differences in efficacy or safety were observed between patients 65 years compared to younger patients. ENHERTU followed by THP: Of the 320 patients with HER2-positive early breast cancer treated with ENHERTU 5.4 mg/kg followed by THP, 12% were 65 years and 1.6% were 75 years. No overall differences in efficacy were observed between patients 65 years compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients 65 years (38%) as compared to younger patients (30%).
* Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min).
* Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, monitor for increased adverse reactions related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).
ting
Positive results from the DESTINY-Lung04 Phase III trial showed AstraZeneca and Daiichi Sankyo's ENHERTU(R) (fam-trastuzumab deruxtecan-nxki) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as a 1st-line treatment of patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer (NSCLC).
Results were presented today during the Presidential Symposium at the IASLC 2026 World Conference on Lung Cancer (#WCLC26) hosted by the International Association for the Study of Lung Cancer in Seoul, South Korea (abstract #PL03.08).
In the primary endpoint of PFS, ENHERTU monotherapy significantly reduced the risk of disease progression or death by 37.0% versus pembrolizumab plus chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.50-0.79; p<0.0001). Median PFS was 14.3 months with ENHERTU compared to 8.3 months for pembrolizumab plus chemotherapy as assessed by blinded independent central review (BICR). A favorable PFS trend was seen for ENHERTU across key subgroups, including the prespecified stratification factors of brain metastases, liver metastases, smoking status, HER2 mutation status (exon 19 or exon 20), and de novo or recurrent disease.
Objective response rate (ORR) with ENHERTU was 70.0% versus 44.5% with pembrolizumab plus chemotherapy. Median duration of response (DoR) for ENHERTU was 13.4 months and 9.7 months with pembrolizumab plus chemotherapy.
Julia Rotow, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute and lead investigator of the trial, said: "HER2-mutant non-small cell lung cancer is an aggressive disease with limited responses to current 1st-line standard of care, and many patients experience disease progression within a year of starting treatment. With seventy percent of patients responding and a median progression-free survival of 14.3 months, trastuzumab deruxtecan has the potential to become an important new 1st-line treatment option for these patients."
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "DESTINY-Lung04 is the first Phase III trial to demonstrate superior progression-free survival versus the global 1st-line standard of care in patients with HER2-mutant advanced non-small cell lung cancer. These results add to the growing body of evidence supporting ENHERTU as an important treatment for patients with HER2 alterations and underscore its potential role at the time of metastatic diagnosis, when treatment has the greatest opportunity to improve outcomes."
John Tsai, Global Head, R&D, Daiichi Sankyo, said: "ENHERTU was the first HER2-directed medicine and antibody drug conjugate approved for patients with HER2-mutant non-small cell lung cancer and has become a second-line standard-of-care treatment. The progression-free survival benefit of six months and strong response rates seen in DESTINY-Lung04 reinforce the importance of targeting HER2 directly in these patients and support the potential of ENHERTU in the 1st-line setting where delaying disease progression for as long as possible is a critical goal."
Summary of results: DESTINY-Lung04i
Efficacy measure ENHERTU
(5.4mg/kg; n=227) Pembrolizumab plus
chemotherapy
(n=227)
PFSii
Median PFS, (months) (95% CI) 14.3
(12.4-16.5) 8.3
(7.0-9.9)
Hazard ratio (95% CI) HR 0.63 (0.50-0.79)
p-value p<0.0001
ORRii,iii
ORR(%) (n)
(95% CI)iv 70.0% (159)
(63.6-75.9) 44.5% (101)
(37.9-51.2)
CR, % (n) 1.8% (4) 1.8% (4)
PR, % (n) 68.3% (155) 42.7% (97)
Median DOR, (months) (95% CI) 13.4
(10.4-17.2) 9.7
(7.0-11.1)
PFS2iii,v
Median PFS2, (months) (95% CI) 22.7
(20.3-26.3) 17.3
(15.6-21.8)
Hazard ratio (95% CI) HR 0.80 (0.62-1.02)
OSvi
Median OS, (months) (95% CI) 29.3
(26.2-33.4) 33.1
(27.7-40.7)
Hazard ratio (95% CI) HR 1.15 (0.88-1.52)
CI, confidence interval; CR, complete response; DOR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response
i Analysis was based on a data cut-off (DCO) of 9 June 2026; median duration of follow-up was 21.6 in the ENHERTU arm and 20.4 months in the pembrolizumab plus chemotherapy arm. At DCO, 40 patients (17.7%) remained in the ENHERTU arm and 10 patients (4.5%) in the pembrolizumab plus chemotherapy arm.
ii Assessed by BICR
iii Assessed by investigator
iv ORR is (CR + PR); includes unconfirmed responses
v PFS2 is defined as the time from randomization to second progression (earliest progression event following first subsequent therapy) or death
vi At DCO, overall data maturity for OS was 46.9% and no formal hypothesis testing was performed; formal hypothesis testing will be performed at the second interim analysis and final analysis
At the time of analysis, the overall survival (OS) data were 46.9% mature and no formal hypothesis testing was performed. While there was no observed benefit in OS, varied and imbalanced subsequent therapy patterns between arms may limit the interpretation of this result. Imbalances include greater use of HER2-directed therapies in the pembrolizumab plus chemotherapy arm versus the ENHERTU arm (48.0% vs 23.3%) and limited use of subsequent immunotherapy plus chemotherapy in the ENHERTU arm (23.8%).
The safety profile of ENHERTU observed in DESTINY-Lung04 was generally consistent with its known profile with no new safety concerns identified.
Despite longer treatment exposure in the ENHERTU arm (median 12.3 months versus 7.1 months), Grade 3 or higher treatment related adverse events (AEs) were comparable between ENHERTU and pembrolizumab plus chemotherapy (34.1% in the ENHERTU arm and 33.6% in the pembrolizumab plus chemotherapy arm). The most common Grade 3 or higher AE occurring in 5% or more of patients treated in both arms was neutropenia (occurring in 11.1% of patients in the ENHERTU arm and 14.1% in the pembrolizumab plus chemotherapy arm). Interstitial lung disease (ILD) or pneumonitis events occurred in 20.8% of patients treated with ENHERTU as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low Grade (Grade 1 [n=7; 3.1%] or Grade 2 [n=30; 13.3%]). There were five Grade 3 (2.2%), one Grade 4 (0.4%) and four Grade 5 (1.8%) ILD events in the ENHERTU arm.
ENHERTU is approved to treat patients with previously treated metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, and to treat patients with HER2-positive solid tumors, including HER2-overexpressing metastatic NSCLC, who have received prior treatment and who have no satisfactory treatment options.
ENHERTU is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
Enhertu U.S. Indications and Important Safety Information
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for:
HER2-Positive Early Breast Cancer
- As neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP)
- As adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment
HER2-Positive Metastatic Breast Cancer
- In combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or, in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
HER2-Low and HER2-Ultralow Metastatic Breast Cancer
- As monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine therapies in the metastatic setting
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy
HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC)
- As monotherapy for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-authorized test, and who have received a prior systemic therapy
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer
- As monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen
HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
- As monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options
This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Important Safety Information
ETCAMAH
Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in 28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., 0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., 1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. In the adjuvant HER2+ breast cancer setting, if drug-induced ILD is suspected, rule out radiotherapy-related pneumonitis. If only radiotherapy-related pneumonitis is suspected, consider interruption of ENHERTU for Grade 2 and permanently discontinue ENHERTU for Grade 3.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), ILD occurred in 12% of patients. Median time to first onset was 8.0 months (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.5% of patients treated with ENHERTU in combination with pertuzumab.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, ILD occurred in 4.4% of patients. Median time to first onset was 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or pneumonitis occurred in 1 patient (0.3%) treated with ENHERTU followed by THP.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3- C or a sustained temperature of 38- C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), decreased neutrophil count occurred in 79% of patients. Median time to first onset was 22 days (range: 5 to 994). Twenty-nine percent had Grade 3 or 4 decreased neutrophil count. Febrile neutropenia was reported in 2.6% of patients.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, a decrease in neutrophil count was reported in 58% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 42 days (range: 11 to 165). Febrile neutropenia was reported in 0.9% of patients.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular dysfunction (LVD) has been observed with anti-HER2 therapies, including ENHERTU. Assess left ventricular ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVD through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
In patients treated with ENHERTU 5.4 mg/kg, LVD was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4.
ENHERTU in Combination with Pertuzumab
In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), LVEF decrease was reported in 11% of patients, of which 2.1% were Grade 3 or 4.
ENHERTU followed by THP
In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, LVD was reported in 1.3% of patients, of which 0.3% were Grade 3.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.
Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level.
Adverse Reactions
HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
ENHERTU as Monotherapy
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for >6 months and 39% were exposed for >1 year. In this pooled safety population, the most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (43%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%).
ENHERTU in Combination with Pertuzumab
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg in combination with pertuzumab intravenously every 3 weeks in 431 patients in DESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381). Among these patients, 86% were exposed for >6 months and 73% were exposed for >1 year. In this pooled safety population, the most common (20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased hemoglobin (80%), decreased neutrophil count (79%), nausea (74%), increased alanine aminotransferase (65%), diarrhea (64%), increased aspartate aminotransferase (63%), decreased lymphocyte count (61%), decreased platelet count (55%), increased blood alkaline phosphatase (54%), decreased blood potassium (54%), fatigue (53%), alopecia (48%), vomiting (46%), upper respiratory tract infection (32%), constipation (31%), decreased appetite (31%), decreased weight (28%), musculoskeletal pain (23%), increased blood bilirubin (23%), and abdominal pain (22%).
HER2-Positive Early Breast Cancer
DESTINY-Breast11
The safety of ENHERTU followed by THP was evaluated in 320 patients with HER2-positive (IHC 3+ or ISH+) early breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11. ENHERTU was administered by intravenous infusion once every three weeks for 4 cycles followed by THP for 4 cycles. The median duration of treatment was 5.6 months (range: 0.7 to 9.1) for patients who recei