RecruitingPhase 3NCT06899126

Study of Trastuzumab Deruxtecan, Pembrolizumab, and Platinum-based Chemotherapy in First-line HER2 Overexpressing Non-small Cell Lung Cancer

A Phase 3, Multicenter, Randomized, Open-label Trial of Trastuzumab Deruxtecan in Combination With Pembrolizumab Versus Platinum-based Chemotherapy in Combination With Pembrolizumab, as First-line Therapy in Participants With Locally Advanced Unresectable or Metastatic HER2 Overexpressing and PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer (DESTINY-Lung06)


Sponsor

Daiichi Sankyo

Enrollment

686 participants

Start Date

Oct 24, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

This clinical trial is designed to assess the efficacy and safety of trastuzumab deruxtecan (T-DXd; Enhertu®) in combination with pembrolizumab versus platinum-based chemotherapy in combination with pembrolizumab in participants with no prior therapy for locally advanced unresectable or metastatic non-squamous NSCLC, whose tumors have HER2-overexpressing and PD-L1 TPS \<50% without known AGA that have locally available therapies targeting their AGAs in first-line advanced/metastatic setting.


Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a combination of three treatments — trastuzumab deruxtecan (T-DXd, an antibody-drug conjugate), pembrolizumab (an immunotherapy drug), and platinum-based chemotherapy — as a first-line treatment for people with advanced non-small cell lung cancer (NSCLC) whose tumors have high levels of HER2 protein. This combination targets HER2 on cancer cells while also boosting the immune response against the tumor. **You may be eligible if...** - You are 18 years or older - You have confirmed stage IV NSCLC (or stage IIIB/IIIC not eligible for surgery or radiation) with a non-squamous cell type - Your tumor has high HER2 overexpression (confirmed by approved testing) - You have not received prior systemic treatment for advanced or metastatic NSCLC - You do not have known actionable genetic mutations (such as EGFR, ALK, or ROS1) that have approved targeted therapies **You may NOT be eligible if...** - Your cancer has squamous cell histology only - You have active or unstable brain metastases (stable brain metastases may be allowed) - You have a history of interstitial lung disease or pneumonitis - You have an active autoimmune condition requiring systemic treatment - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGTrastuzumab Deruxtecan

T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)

DRUGpembrolizumab

pembrolizumab will be administered at a dose of 200 mg IV Q3W

DRUGPemetrexed

Pemetrexed will be administered at a dose of 500 mg/m2 IV Q3W

DRUGChemotherapy

One of the following two will be administered in Arm B: Cisplatin at a dose of 75 mg/m2 IV or carboplatin AUC at a dose of 5 mg/mL/min IV


Locations(100)

Alaska Oncology & Hematology, LLC

Anchorage, Alaska, United States

Orange Coast Memorial Medical Center Fountain Valley

Fountain Valley, California, United States

California Research Institute

Los Angeles, California, United States

Los Angeles Cancer Network (LACN)

Los Angeles, California, United States

Providence Medical Foundation

Santa Rosa, California, United States

Bay Pines VA Healthcare System

Bay Pines, Florida, United States

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Mid-Florida Hematology & Oncology Centers, P.A.

Orange City, Florida, United States

BRCR Global Plantation

Plantation, Florida, United States

Hope and Healing Cancer Services

Hinsdale, Illinois, United States

Logan Health Research

Kalispell, Montana, United States

Clinical Research Alliance

Westbury, New York, United States

FirstHealth Cancer Center

Pinehurst, North Carolina, United States

Gabrail Cancer Center

Canton, Ohio, United States

St. Charles Health System

Bend, Oregon, United States

University of Texas M. D. Anderson Cancer Center

Houston, Texas, United States

Lumi Research

Kingwood, Texas, United States

Summit Cancer Treatment Center

Spokane, Washington, United States

CINME - Centro De Investigaciones Metabolicas

Buenos Aires, Argentina

Instituto Argentino de Diagnostico y Tratamiento

Buenos Aires, Argentina

Instituto de Investigaciones Metabolicas (IDIM)

Buenos Aires, Argentina

Instituto Medico de la Fundacion Estudios Clinicos

Rosario, Argentina

CHU Helora-Hospital de Mons

Mons, Belgium

Hospital de Cancer de Barretos - Fundacao Pio XII

Barretos, Brazil

Centro de Pesquisas Clinica Reichow

Blumenau, Brazil

CIONC-Centro Integrado de Oncologia de Curitiba

Curitiba, Brazil

CRIO - Centro Regional Integrado de Oncologia

Fortaleza, Brazil

Liga Norte-Rio-Grandense Contra o Câncer

Natal, Brazil

Hospital Ernesto Dornelles

Porto Alegre, Brazil

Hospital São Lucas da PUCRS

Porto Alegre, Brazil

Centro de Tratamento Oncologico (CTO)

Ribeirão Preto, Brazil

Hospital das Clínicas FMRP-USP

Ribeirão Preto, Brazil

Obras Sociais Irmã Dulce - Hospital Santo Antônio

Salvador, Brazil

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

Sao Jose Rio Preto, Brazil

Centro Paulista de Oncologia S A

Vila Olímpia, Brazil

China-Japan Friendship hospital

Beijing, China

The First Hospital of Jilin University

Changchun, China

Sichuan Cancer Hospital

Chengdu, China

West China Hospital, Sichuan University

Chengdu, China

Chongqing University Cancer Hospital

Chongqing, China

Nanfang Hospital of Southern Medical University

Guangzhou, China

Sir Run Run Shaw Hospital of Zhejiang University School of Medicine

Hangzhou, China

Harbin Medical University Cancer Hospital

Harbin, China

The Second Hospital of Anhui Medical University

Hefei, China

Hong Kong Integrated Oncology Centre

Hong Kong, China

Cancer Hospital of Shandong First Medical University

Jinan, China

Hong Kong United Oncology Centre

Jordan, China

Linyi Cancer Hospital

Linyi, China

The First Affiliated Hospital of Nanchang University

Nanchang, China

The Second Affiliated Hospital of Nanchang University

Nanchang, China

Jiangsu Province Hospital

Nanjing, China

The Second People's Hospital of Neijiang

Neijiang, China

Shanghai East Hospital

Shanghai, China

Liaoning Cancer Hospital & Institute

Shenyang, China

Shanxi Provincial Cancer Hospital

Taiyuan, China

Tianjin Medical University General Hospital

Tianjin, China

Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

Xiangyang Central Hospital

Xiangyang, China

Hopital Albert Calmette - CHU Lille

Lille, France

Saitama Medical University International Medical Center

Hidaka-shi, Japan

Kansai Medical University Hospital

Hirakata-shi, Japan

Hirosaki University Hospital

Hirosaki-shi, Japan

St. Marianna University Hospital

Kawasaki-shi, Japan

Hospital of the University of Occupational and Environmental Health

Kitakyushu-shi, Japan

Saiseikai Kumamoto Hospital

Kumamoto, Japan

Kurume University Hospital

Kurume-shi, Japan

Matsusaka Municipal Hospital

Matsusaka-shi, Japan

NHO Okayama Medical Center

Okayama, Japan

Osaka City General Hospital

Osaka, Japan

Osaka International Cancer Institute

Osaka, Japan

NHO Kinki-Chuo Chest Medical Center

Sakaishi, Japan

Keijinkai Teine Keijinkai Hospital

Sapporo, Japan

Tokyo Medical University Hospital

Shinjuku-ku, Japan

Shizuoka Cancer Center

Sunto-gun, Japan

Fujita Health University Hospital

Toyoake-shi, Japan

Wakayama Medical University Hospital

Wakayama, Japan

Kanagawa Cancer Center

Yokohama, Japan

Tottori University Hospital

Yonago-shi, Japan

Hospital Kuala Lumpur

Kuala Lumpur, Malaysia

Hospital Tengku Ampuan Afzan

Kuantan, Malaysia

Beacon Hospital Sdn Bhd

Petaling Jaya, Malaysia

Unidade Local de Saude de Santa Maria, E.P.E. - Hospital Pulido Valente

Lisbon, Portugal

National Cancer Center

Goyang-si, South Korea

Gyeongsang National University Hospital

Jinju, South Korea

CHA Bundang Medical Center, CHA University

Seongnam, South Korea

Seoul National University Bundang Hospital

Seongnam, South Korea

Asan Medical Center

Seoul, South Korea

Samsung Medical Center

Seoul, South Korea

Severance Hospital, Yonsei University Health System

Seoul, South Korea

The Catholic University of Korea, St. Vincent's Hospital

Suwon, South Korea

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Taichung Veterans General Hospital

Taichung, Taiwan

Chi Mei Hospital, Liouying

Tainan, Taiwan

National Cheng Kung University Hospital

Tainan, Taiwan

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

Tri-Service General Hospital

Taipei, Taiwan

Chang Gung Memorial Hospital,Linkou

Taoyuan City, Taiwan

Charing Cross Hospital

London, United Kingdom

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NCT06899126


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