RECRUITING Phase 3 ClinicalTrials.gov

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

Sponsor: Daiichi Sankyo • ClinicalTrials.gov ID: NCT06899126

Registry updated: 2026-09-15

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Description

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.

Interventions

Trastuzumab Deruxtecan (Drug)
T-DXd will be administered at a dose of 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W)
pembrolizumab (Drug)
pembrolizumab will be administered at a dose of 200 mg IV Q3W
Pemetrexed (Drug)
Pemetrexed will be administered at a dose of 500 mg/m\^2 IV Q3W
Platinum Chemotherapy (Drug)
One of the following two will be administered in Arm B: Cisplatin at a dose of 75 mg/m\^2 IV or carboplatin AUC at a dose of 5 mg/mL/min IV Q3W

Eligibility criteria

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 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 the local test results obtained using validated or approved tests as required per local regulation) 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 non-squamous NSCLC 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 if their disease has progressed at least 6 months after 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 must be ruled out for MI. It is highly recommended that the investigator refer such participants for a cardiologic consultation during the Screening Period. 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 clinically severe pulmonary compromise resulting from intercurrent, pulmonary illnesses including, but not limited to: 1. Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the trial randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion). 2. Any auto immune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis). Severe conditions are those defined as impacting daily activities and/or requiring use of supplemental oxygen. 5. Had a prior complete pneumonectomy.

Conditions

Non-small Cell Lung Cancer

Locations

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
Lynn Cancer Institute Center — Boca Raton, 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
Cleveland Clinic Florida - Weston — Weston, Florida, United States
Piedmont Cancer Institute OneOncology — Atlanta, Georgia, United States
The Queens Medical Center — Honolulu, Hawaii, United States
Hope and Healing Cancer Services — Hinsdale, Illinois, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States
Mayo Clinic — Rochester, Minnesota, United States
Logan Health Research — Kalispell, Montana, United States
Renown Regional Medical Center — Reno, Nevada, United States
Clinical Research Alliance — Westbury, New York, United States
FirstHealth Cancer Center — Pinehurst, North Carolina, United States
Carolina Cancer Research Center — Wilson, 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
Hospital Italiano de Buenos Aires — Buenos Aires, Argentina
Instituto Argentino de Diagnostico y Tratamiento — Buenos Aires, Argentina
Instituto de Investigaciones Metabolicas (IDIM) — Buenos Aires, Argentina
Centro de Investigaciones Medicas y Desarrollo LC SRL (LC Investigacion) — Ciudad Autonoma Buenos Aires, Argentina
Instituto de Investigaciones Clinicas Cordoba S.A. — Córdoba, Argentina
Centro de Investigacion Pergamino SA — Pergamino, Argentina
Hospital Universitario Austral — Pilar, Argentina
Sanatorio Britanico S.A. — Rosario, Argentina
Instituto de Oncologia de Rosario — Rosario, Argentina
Instituto Medico de la Fundacion Estudios Clinicos — Rosario, Argentina
Sanatorio Parque S.A. — Rosario, Argentina
Instituto San Marcos — San Juan, Argentina
UZA — Edegem, Belgium
Grand Hôpital de Charleroi-Les Viviers — Gilly, Belgium
Chu Helora Hospital La Louvière Site Jolimont — La Louvière, Belgium
Chu de Liăge — Liège, Belgium
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
Hospital Nossa Senhora Da Conceição — Porto Alegre, Brazil
Centro de Tratamento Oncologico (CTO) — Ribeirão Preto, Brazil
Hospital das Clínicas FMRP-USP — Ribeirão Preto, Brazil
Oncoclínicas Rio de Janeiro — Rio de Janeiro, Brazil
Instituto Dâor Pesquisa E Ensino - Rio de Janeiro — Rio de Janeiro, 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
Icesp - Instituto Do Câncer Do Estado de São Paulo Octavio Frias de Oliveira — São Paulo, Brazil
Centro Paulista de Oncologia S A — Vila Olímpia, Brazil
Biocenter — Concepción, Chile
Orlandi Oncologia — Santiago, Chile
Centro de Oncologia de Precision — Santiago, Chile
Hospital Clinico Universidad de Chile — Santiago, Chile
Centro de Investigacion Clinica Bradford Hill — Santiago, Chile
Clinica Redsalud Vitacura — Santiago, Chile
Beijing Cancer Hospital — Beijing, China
China-Japan Friendship hospital — Beijing, China
Jilin Cancer Hospital — Changchun, China
The First Hospital of Jilin University — Changchun, China
Hunan Cancer Hospital — Changsha, 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
Anhui Provincial Hospital — Hefei, 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
The First Hospital of China Medical University — Shenyang, China
Liaoning Cancer Hospital & Institute — Shenyang, China
Shanxi Provincial Cancer Hospital — Taiyuan, China
Tianjin Medical University General Hospital — Tianjin, China
Hubei Cancer Hospital — Wuhan, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology — Wuhan, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology — Wuhan, China
Xiangyang Central Hospital — Xiangyang, China
Henan Cancer Hospital — Zhengzhou, China
CHU Angers - Hôpital Larrey — Angers, France
Institut Bergonié — Bordeaux, France
Hăpital Ambroise Pară — Boulogne-Billancourt, France
Hospices Civils de Lyon — Bron, France
Centre Hospitalier Intercommunal de Créteil — Créteil, France
Centre Georges Francois Leclerc — Dijon, France
Hopital Albert Calmette - CHU Lille — Lille, France
Centre Leon Berard — Lyon, France
Assistance Publique-Hôpitaux de Marseille — Marseille, France
Clinique Clementville — Montpellier, France
Hăpital Privă Du Confluent — Nantes, France
Hopital Bichat - Claude Bernard — Paris, France
Chu Nantes - Hăpital Guillaume Et Renă Laă Nnec — Saint-Herblain, France
Institut de Cancerologie de L'Ouest — Saint-Herblain, France
Hăpital Foch — Suresnes, France
Hopital Larrey — Toulouse, France
Universitatsmedizin Mainz — Essen, Germany
Klinikum Esslingen GmbH — Esslingen am Neckar, Germany
Universitaetsmedizin Mannheim — Manheim, Germany
Universtitaetsklinikum Essen — Nordrhein Westfalen, Germany
General Hospital of Athens of Chest Diseases "SOTIRIA" — Athens, Greece
'Henry Dynant' Hospital Center — Athens, Greece
National and Kapodistrian University of Athens (Nkua)-University General Hospital Attikon — Athens, Greece
University General Hospital of Larissa — Larissa, Greece
Metropolitan Hospital — Neo Faliro, Greece
St Luke's Hospital — Panórama, Greece
University General Hospital of Patras — Pátrai, Greece
Special Anticancer Hospital of Piraeus 'Metaxa' — Piraeus, Greece
General Hospital Papageorgiou — Thessaloniki, Greece
Interbalkan Hospital of Thessaloniki — Thessaloniki, Greece
Queen Elizabeth Hospital — Hong Kong, Hong Kong
The University of Hong Kong — Hong Kong, Hong Kong
The Chinese University of Hong Kong — Shatin, Hong Kong
Gleneagles Hospital Hong Kong — Wong Chuk Hang, Hong Kong
Mazumdar Shaw Medical Center — Bangalore, India
All India Institute of Medical Sciences — Bhubaneswar, India
Narayana Superspeciality Hospital — Howrah, India
Yenepoya Medical College Hospital — Mangalore, India
Deenanath Mangeshkar Hospital and Research Centre — Pune, India
Nirmal Hospital Private Limited — Surat, India
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi Irccs — Bologna, Italy
Fondazione del Piemonte per l'Oncologia IRCCS Candiolo — Candiolo, Italy
Ospedale Santa Croce — Fano, Italy
Istituto Nazionale Per La Ricerca Sul Cancro Di Genova — Genova, Italy
Presidio Ospedaliero Di Livorno — Livorno, Italy
Ospedale San Raffaele — Milan, Italy
Humanitas Istituto Clinico Catanese — Misterbianco, Italy
Azienda Ospedaliero-Universitaria S.Luigi Gonzaga — Orbassano, Italy
Azienda Ospedaliera S.Giovanni Addolorata — Roma, Italy
Istituto Nazionale Tumori Regina Elena IRCCS — Roma, Italy
Centro Ricerche Cliniche di Verona s.r.l. — Verona, Italy
Saitama Medical University International Medical Center — Hidaka-shi, Japan
Kansai Medical University Hospital — Hirakata-shi, Japan
Hirosaki University Hospital — Hirosaki-shi, Japan
National Cancer Center Hospital East — Kashiwa-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
Toho University Omori Medical Center — Ōta-ku, 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
Ehime University Hospital — Toon-shi, 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
Gleneagles Hospital Penang — Jalan Pangkor, Malaysia
Hospital Kuala Lumpur — Kuala Lumpur, Malaysia
Hospital Tengku Ampuan Afzan — Kuantan, Malaysia
Beacon Hospital Sdn Bhd — Petaling Jaya, Malaysia
Wojewodzki Szpital Im. SW. Ojca Pio W Przemyslu — Rzeszów, Poland
Hospital da Luz — Lisbon, Portugal
Unidade Local de Saude de Santa Maria, E.P.E. - Hospital Pulido Valente — Lisbon, Portugal
Centro Hospitalar do Porto, E.P.E. - Hospital de Santo António — Porto, Portugal
Hospital CUF Porto — Porto, Portugal
Delta Health Care S.R.L — Bucharest, Romania
Colentina Hospital — Bucharest, Romania
Memorial Healthcare International S R L — Bucharest, Romania
Institutul Oncologic — Cluj-Napoca, Romania
Spitalul Clinic Militar de Urgenta Dr. "Constantin Papilian" Cluj-Napoca — Cluj-Napoca, Romania
Centrul de Oncologie Sfantul Nectarie Craiova — Craiova, Romania
Institutul Regional de Oncologie Lasi — Lasi, Romania
S.C R.T.C Radiology Therapeutic Center S.R.L — Otopeni, Romania
Spitalul Municipal Ploiesti — Ploieşti, Romania
Chungbuk National University Hospital — Cheongju-si, South Korea
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
Severance Hospital, Yonsei University Health System — Seoul, South Korea
Asan Medical Center — Seoul, South Korea
Samsung Medical Center — Seoul, South Korea
The Catholic University of Korea, St. Vincent's Hospital — Suwon, South Korea
Complejo Hospitalario Universitario A Coruna — A Coruña, Spain
Hospital del Mar — Barcelona, Spain
Hospital Clinic de Barcelona — Barcelona, Spain
ICO l'Hospitalet - Hospital Duran i Reynals — Barcelona, Spain
Hospital Universitari Dexeus — Barcelona, Spain
Hospital Universitari Vall d'Hebron - VHIO — Barcelona, Spain
Complejo Asistencial Universitario de Burgos — Burgos, Spain
Hospital Provincial de Castellon — Castellion, Spain
Complejo Hospitalario Universitario Insular-Materno Infantil — Las Palmas de Gran Canaria, Spain
Hospital Universitario Lucus Augusti — Lugo, Spain
Hospital General Universitario Gregorio Marañon — Madrid, Spain
Hospital Universitario 12 de Octubre — Madrid, Spain
Hospital Universitario La Paz — Madrid, Spain
Hospital Universitario Clinico San Carlos — Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria — Málaga, Spain
Hospital Regional Universitario de Malaga — Málaga, Spain
Hospital Universitario Central de Asturias — Oviedo, Spain
Complejo Hospitalario Universitario de Santiago — Santiago de Compostela, Spain
Hospital Universitario Nuestra Señora de Valme — Seville, Spain
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
National Taiwan University Cancer Center — Taipei, 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
Siriraj Hospital — Bangkok, Thailand
Phramongkutklao Hospital — Bangkok, Thailand
Vajira Hospital — Dusit, Thailand
Songklanagarind Hospital — Hat Yai, Thailand
Chulabhorn Hospital — Laksi, Thailand
Rajavithi Hospital — Rajathevee, Thailand
Medical Park Seyhan Hospital — Adana, Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Ankara Oncology Research and Training Hospital, Clinical Research Center — Ankara, Turkey (Türkiye)
Gulhane Training and Research Hospital — Ankara, Turkey (Türkiye)
Hacettepe University Medical Faculty — Ankara, Turkey (Türkiye)
Medipol University Medical Faculty — Istanbul, Turkey (Türkiye)
Goztepe Prof. Dr. Suleyman Yalcin City Hospital — Istanbul, Turkey (Türkiye)
Eastbourne District General Hospital — Eastbourne, United Kingdom
Charing Cross Hospital — London, United Kingdom
Altnagelvin Area Hospital — Londonderry, United Kingdom
Nottingham University Hospitals City Campus — Nottingham, United Kingdom

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Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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