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

NCT ID: NCT06899126

Last Updated: 2026-01-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

686 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-24

Study Completion Date

2032-07-05

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Non-small Cell Lung Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

This is an open-label study.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Arm A: T-DXd

Participants will receive T-DXd plus pembrolizumab

Group Type EXPERIMENTAL

Trastuzumab Deruxtecan

Intervention Type DRUG

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

pembrolizumab

Intervention Type DRUG

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

Arm B: Pemetrexed + Chemotherapy + Pembrolizumab

Participants will receive Pemetrexed plus platinum chemotherapy (cisplatin or carboplatin) plus pembrolizumab

Group Type ACTIVE_COMPARATOR

pembrolizumab

Intervention Type DRUG

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

Pemetrexed

Intervention Type DRUG

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

Chemotherapy

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Trastuzumab Deruxtecan

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

Intervention Type DRUG

pembrolizumab

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

Intervention Type DRUG

Pemetrexed

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

Intervention Type DRUG

Chemotherapy

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

T-DXd ENHERTU® DS-8201a KEYTRUDA®

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. 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.
2. 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.
3. 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.
4. 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.

1. Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I.
2. HER2-targeted antibody-based anticancer therapy.
5. 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.

Exclusion Criteria

1. 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.
2. Has a QTc prolongation to \>480 ms based on the average of the Screening triplicate 12- lead ECG.
3. 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.
4. 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.).
5. Had a prior complete pneumonectomy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Alaska Oncology & Hematology, LLC

Anchorage, Alaska, United States

Site Status RECRUITING

Orange Coast Memorial Medical Center Fountain Valley

Fountain Valley, California, United States

Site Status RECRUITING

California Research Institute

Los Angeles, California, United States

Site Status RECRUITING

Los Angeles Cancer Network (LACN)

Los Angeles, California, United States

Site Status RECRUITING

Providence Medical Foundation

Santa Rosa, California, United States

Site Status RECRUITING

Bay Pines VA Healthcare System

Bay Pines, Florida, United States

Site Status RECRUITING

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Site Status RECRUITING

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

Orange City, Florida, United States

Site Status RECRUITING

BRCR Global Plantation

Plantation, Florida, United States

Site Status RECRUITING

Hope and Healing Cancer Services

Hinsdale, Illinois, United States

Site Status RECRUITING

Logan Health Research

Kalispell, Montana, United States

Site Status RECRUITING

Clinical Research Alliance

Westbury, New York, United States

Site Status ACTIVE_NOT_RECRUITING

FirstHealth Cancer Center

Pinehurst, North Carolina, United States

Site Status RECRUITING

Gabrail Cancer Center

Canton, Ohio, United States

Site Status RECRUITING

St. Charles Health System

Bend, Oregon, United States

Site Status RECRUITING

University of Texas M. D. Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Lumi Research

Kingwood, Texas, United States

Site Status RECRUITING

Summit Cancer Treatment Center

Spokane, Washington, United States

Site Status RECRUITING

CINME - Centro De Investigaciones Metabolicas

Buenos Aires, , Argentina

Site Status RECRUITING

Instituto Argentino de Diagnostico y Tratamiento

Buenos Aires, , Argentina

Site Status RECRUITING

Instituto de Investigaciones Metabolicas (IDIM)

Buenos Aires, , Argentina

Site Status RECRUITING

Instituto Medico de la Fundacion Estudios Clinicos

Rosario, , Argentina

Site Status RECRUITING

CHU Helora-Hospital de Mons

Mons, , Belgium

Site Status RECRUITING

Hospital de Cancer de Barretos - Fundacao Pio XII

Barretos, , Brazil

Site Status RECRUITING

Centro de Pesquisas Clinica Reichow

Blumenau, , Brazil

Site Status RECRUITING

CIONC-Centro Integrado de Oncologia de Curitiba

Curitiba, , Brazil

Site Status RECRUITING

CRIO - Centro Regional Integrado de Oncologia

Fortaleza, , Brazil

Site Status RECRUITING

Liga Norte-Rio-Grandense Contra o Câncer

Natal, , Brazil

Site Status RECRUITING

Hospital Ernesto Dornelles

Porto Alegre, , Brazil

Site Status RECRUITING

Hospital São Lucas da PUCRS

Porto Alegre, , Brazil

Site Status RECRUITING

Centro de Tratamento Oncologico (CTO)

Ribeirão Preto, , Brazil

Site Status RECRUITING

Hospital das Clínicas FMRP-USP

Ribeirão Preto, , Brazil

Site Status RECRUITING

Obras Sociais Irmã Dulce - Hospital Santo Antônio

Salvador, , Brazil

Site Status RECRUITING

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, , Brazil

Site Status RECRUITING

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

Sao Jose Rio Preto, , Brazil

Site Status RECRUITING

Centro Paulista de Oncologia S A

Vila Olímpia, , Brazil

Site Status RECRUITING

China-Japan Friendship hospital

Beijing, , China

Site Status RECRUITING

The First Hospital of Jilin University

Changchun, , China

Site Status RECRUITING

Sichuan Cancer Hospital

Chengdu, , China

Site Status RECRUITING

West China Hospital, Sichuan University

Chengdu, , China

Site Status RECRUITING

Chongqing University Cancer Hospital

Chongqing, , China

Site Status RECRUITING

Nanfang Hospital of Southern Medical University

Guangzhou, , China

Site Status RECRUITING

Sir Run Run Shaw Hospital of Zhejiang University School of Medicine

Hangzhou, , China

Site Status RECRUITING

Harbin Medical University Cancer Hospital

Harbin, , China

Site Status RECRUITING

The Second Hospital of Anhui Medical University

Hefei, , China

Site Status RECRUITING

Hong Kong Integrated Oncology Centre

Hong Kong, , China

Site Status RECRUITING

Cancer Hospital of Shandong First Medical University

Jinan, , China

Site Status RECRUITING

Hong Kong United Oncology Centre

Jordan, , China

Site Status RECRUITING

Linyi Cancer Hospital

Linyi, , China

Site Status RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, , China

Site Status RECRUITING

The Second Affiliated Hospital of Nanchang University

Nanchang, , China

Site Status RECRUITING

Jiangsu Province Hospital

Nanjing, , China

Site Status RECRUITING

The Second People's Hospital of Neijiang

Neijiang, , China

Site Status RECRUITING

Shanghai East Hospital

Shanghai, , China

Site Status RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, , China

Site Status RECRUITING

Shanxi Provincial Cancer Hospital

Taiyuan, , China

Site Status RECRUITING

Tianjin Medical University General Hospital

Tianjin, , China

Site Status RECRUITING

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

Wuhan, , China

Site Status RECRUITING

Xiangyang Central Hospital

Xiangyang, , China

Site Status RECRUITING

Hopital Albert Calmette - CHU Lille

Lille, , France

Site Status RECRUITING

Saitama Medical University International Medical Center

Hidaka-shi, , Japan

Site Status RECRUITING

Kansai Medical University Hospital

Hirakata-shi, , Japan

Site Status RECRUITING

Hirosaki University Hospital

Hirosaki-shi, , Japan

Site Status RECRUITING

St. Marianna University Hospital

Kawasaki-shi, , Japan

Site Status RECRUITING

Hospital of the University of Occupational and Environmental Health

Kitakyushu-shi, , Japan

Site Status RECRUITING

Saiseikai Kumamoto Hospital

Kumamoto, , Japan

Site Status RECRUITING

Kurume University Hospital

Kurume-shi, , Japan

Site Status RECRUITING

Matsusaka Municipal Hospital

Matsusaka-shi, , Japan

Site Status RECRUITING

NHO Okayama Medical Center

Okayama, , Japan

Site Status RECRUITING

Osaka City General Hospital

Osaka, , Japan

Site Status RECRUITING

Osaka International Cancer Institute

Osaka, , Japan

Site Status RECRUITING

NHO Kinki-Chuo Chest Medical Center

Sakaishi, , Japan

Site Status RECRUITING

Keijinkai Teine Keijinkai Hospital

Sapporo, , Japan

Site Status RECRUITING

Tokyo Medical University Hospital

Shinjuku-ku, , Japan

Site Status RECRUITING

Shizuoka Cancer Center

Sunto-gun, , Japan

Site Status RECRUITING

Fujita Health University Hospital

Toyoake-shi, , Japan

Site Status RECRUITING

Wakayama Medical University Hospital

Wakayama, , Japan

Site Status RECRUITING

Kanagawa Cancer Center

Yokohama, , Japan

Site Status RECRUITING

Tottori University Hospital

Yonago-shi, , Japan

Site Status RECRUITING

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Site Status RECRUITING

Hospital Tengku Ampuan Afzan

Kuantan, , Malaysia

Site Status RECRUITING

Beacon Hospital Sdn Bhd

Petaling Jaya, , Malaysia

Site Status RECRUITING

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

Lisbon, , Portugal

Site Status RECRUITING

National Cancer Center

Goyang-si, , South Korea

Site Status RECRUITING

Gyeongsang National University Hospital

Jinju, , South Korea

Site Status RECRUITING

CHA Bundang Medical Center, CHA University

Seongnam, , South Korea

Site Status RECRUITING

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status RECRUITING

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

Suwon, , South Korea

Site Status RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status RECRUITING

Chi Mei Hospital, Liouying

Tainan, , Taiwan

Site Status RECRUITING

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status RECRUITING

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Tri-Service General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Chang Gung Memorial Hospital,Linkou

Taoyuan, , Taiwan

Site Status RECRUITING

Charing Cross Hospital

London, , United Kingdom

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Belgium Brazil China France Japan Malaysia Portugal South Korea Taiwan United Kingdom

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Contact for Trial Information

Role: CONTACT

908-992-6400

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2024-515658-26-00

Identifier Type: CTIS

Identifier Source: secondary_id

KEYNOTE-G23

Identifier Type: OTHER

Identifier Source: secondary_id

MK-3475-G23

Identifier Type: OTHER

Identifier Source: secondary_id

DS8201-793

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.