Study of Trastuzumab Deruxtecan, Pembrolizumab, and Platinum-based Chemotherapy in First-line HER2 Overexpressing Non-small Cell Lung Cancer
DESTINY-Lung06
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)
4 other identifiers
interventional
686
12 countries
100
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 nonsmall-cell-lung-cancer
Started Oct 2025
Typical duration for phase_3 nonsmall-cell-lung-cancer
100 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 21, 2025
CompletedFirst Posted
Study publicly available on registry
March 27, 2025
CompletedStudy Start
First participant enrolled
October 24, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 5, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 5, 2032
January 8, 2026
January 1, 2026
4.4 years
March 21, 2025
January 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival by Blinded Independent Central Review
PFS is defined as the time interval from the date of randomization to the date of radiographic disease progression or death due to any cause. Tumor response will be determined by BICR assessment of tumor scans using RECIST v1.1.
From date of randomization to the date of radiographic disease progression or death due to any cause, up to 54 months
Secondary Outcomes (1)
Overall Survival
From date of randomization to the date of death due to any cause, up to 85 months
Study Arms (2)
Arm A: T-DXd
EXPERIMENTALParticipants will receive T-DXd plus pembrolizumab
Arm B: Pemetrexed + Chemotherapy + Pembrolizumab
ACTIVE COMPARATORParticipants will receive Pemetrexed plus platinum chemotherapy (cisplatin or carboplatin) plus pembrolizumab
Interventions
Pemetrexed will be administered at a dose of 500 mg/m2 IV Q3W
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
T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)
pembrolizumab will be administered at a dose of 200 mg IV Q3W
Eligibility Criteria
You may qualify if:
- Sign and date the Tissue Screening ICF, prior to any Tissue Screening procedure. Sign and date the Main ICF, prior to the start of any trial-specific qualification procedures.
- Sign and date the Optional PGx ICF (included in the Main Screening ICF) prior to any PGx procedure, and the Pregnant Partner ICF, if applicable.
- Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old.
- Histologically documented non-squamous locally advanced unresectable or metastatic
- NSCLC and meets all of the following criteria:
- Has Stage IV NSCLC disease or Stage IIIB or IIIC disease but is not a candidate for surgical resection or definitive chemoradiation at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition). Has no known AGAs (based on existing test result of local test) that have locally available therapies targeting their AGAs in the first-line advanced/metastatic setting. Has no known HER2 mutation based on existing test results (if approved or validated local test is available). Note: Participants with mixed histology are eligible if adenocarcinoma is the predominant histology. Mixed tumors will be classified based on the predominant cell type.
- Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Participants who received adjuvant or neoadjuvant therapy other than those listed below, including ICI (ie, anti-PD-1/PD-L1) or a platinum-based regimen, are eligible if the last dose of adjuvant/neoadjuvant therapy was given at least 6 months before the date of the first trial dose and should not have progressed on or within 6 months of the last dose date of adjuvant/neoadjuvant therapy.
- Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I.
- HER2-targeted antibody-based anticancer therapy.
- Has adequate tumor tissue sample (not previously irradiated) available for assessment of HER2 and PD-L1 expression by central or Sponsor-specified laboratory. A new biopsy is required if the participant's most recent archival tumor tissue sample cannot be supplied.
- Details pertaining to tumor tissue submission can be found in the Trial Laboratory Manual.
You may not qualify if:
- Has a medical history of MI within 6 months before randomization/enrollment or symptomatic CHF (NYHA Class II to Class IV). Participants with troponin levels above the ULN at Screening (as defined by the manufacturer) and without any MI-related symptoms should have a cardiologic consultation during the Screening Period to rule out MI.
- Has a QTc prolongation to \>480 ms based on the average of the Screening triplicate 12- lead ECG.
- Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- Has lung-specific, intercurrent, clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the trial randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.).
- Had a prior complete pneumonectomy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Merck Sharp & Dohme LLCcollaborator
- Daiichi Sankyolead
Study Sites (100)
Alaska Oncology & Hematology, LLC
Anchorage, Alaska, 99508, United States
Orange Coast Memorial Medical Center Fountain Valley
Fountain Valley, California, 97208, United States
California Research Institute
Los Angeles, California, 90027, United States
Los Angeles Cancer Network (LACN)
Los Angeles, California, 91204, United States
Providence Medical Foundation
Santa Rosa, California, 95403, United States
Bay Pines VA Healthcare System
Bay Pines, Florida, 33744, United States
Holy Cross Hospital
Fort Lauderdale, Florida, 33308, United States
Mid-Florida Hematology & Oncology Centers, P.A.
Orange City, Florida, 33763, United States
BRCR Global Plantation
Plantation, Florida, 33321, United States
Hope and Healing Cancer Services
Hinsdale, Illinois, 60521, United States
Logan Health Research
Kalispell, Montana, 59901, United States
Clinical Research Alliance
Westbury, New York, 11590, United States
FirstHealth Cancer Center
Pinehurst, North Carolina, 28374, United States
Gabrail Cancer Center
Canton, Ohio, 44718, United States
St. Charles Health System
Bend, Oregon, 97701, United States
University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030, United States
Lumi Research
Kingwood, Texas, 77339, United States
Summit Cancer Treatment Center
Spokane, Washington, 99208, 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 CĂ¢ncer
Natal, Brazil
Hospital Ernesto Dornelles
Porto Alegre, Brazil
Hospital SĂ£o Lucas da PUCRS
Porto Alegre, Brazil
Centro de Tratamento Oncologico (CTO)
RibeirĂ£o Preto, Brazil
Hospital das ClĂnicas FMRP-USP
RibeirĂ£o Preto, Brazil
Obras Sociais IrmĂ£ Dulce - Hospital Santo AntĂ´nio
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 OlĂmpia, 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, Taiwan
Charing Cross Hospital
London, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- This is an open-label study.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 21, 2025
First Posted
March 27, 2025
Study Start
October 24, 2025
Primary Completion (Estimated)
March 5, 2030
Study Completion (Estimated)
July 5, 2032
Last Updated
January 8, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
- Access Criteria
- Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/