Actively Recruiting
Study of Trastuzumab Deruxtecan, Pembrolizumab, and Platinum-based Chemotherapy in First-line HER2 Overexpressing Non-small Cell Lung Cancer
Led by Daiichi Sankyo · Updated on 2026-01-08
686
Participants Needed
100
Research Sites
349 weeks
Total Duration
On this page
Sponsors
D
Daiichi Sankyo
Lead Sponsor
M
Merck Sharp & Dohme LLC
Collaborating Sponsor
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Study of Trastuzumab Deruxtecan, Pembrolizumab, and Platinum-based Chemotherapy in First-line HER2 Overexpressing Non-small Cell Lung Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
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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.
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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.
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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.
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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.
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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 will not qualify if you...
- 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.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 100 locations
1
Alaska Oncology & Hematology, LLC
Anchorage, Alaska, United States, 99508
Actively Recruiting
2
Orange Coast Memorial Medical Center Fountain Valley
Fountain Valley, California, United States, 97208
Actively Recruiting
3
California Research Institute
Los Angeles, California, United States, 90027
Actively Recruiting
4
Los Angeles Cancer Network (LACN)
Los Angeles, California, United States, 91204
Actively Recruiting
5
Providence Medical Foundation
Santa Rosa, California, United States, 95403
Actively Recruiting
6
Bay Pines VA Healthcare System
Bay Pines, Florida, United States, 33744
Actively Recruiting
7
Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
Actively Recruiting
8
Mid-Florida Hematology & Oncology Centers, P.A.
Orange City, Florida, United States, 33763
Actively Recruiting
9
BRCR Global Plantation
Plantation, Florida, United States, 33321
Actively Recruiting
10
Hope and Healing Cancer Services
Hinsdale, Illinois, United States, 60521
Actively Recruiting
11
Logan Health Research
Kalispell, Montana, United States, 59901
Actively Recruiting
12
Clinical Research Alliance
Westbury, New York, United States, 11590
Active, Not Recruiting
13
FirstHealth Cancer Center
Pinehurst, North Carolina, United States, 28374
Actively Recruiting
14
Gabrail Cancer Center
Canton, Ohio, United States, 44718
Actively Recruiting
15
St. Charles Health System
Bend, Oregon, United States, 97701
Actively Recruiting
16
University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
17
Lumi Research
Kingwood, Texas, United States, 77339
Actively Recruiting
18
Summit Cancer Treatment Center
Spokane, Washington, United States, 99208
Actively Recruiting
19
CINME - Centro De Investigaciones Metabolicas
Buenos Aires, Argentina
Actively Recruiting
20
Instituto Argentino de Diagnostico y Tratamiento
Buenos Aires, Argentina
Actively Recruiting
21
Instituto de Investigaciones Metabolicas (IDIM)
Buenos Aires, Argentina
Actively Recruiting
22
Instituto Medico de la Fundacion Estudios Clinicos
Rosario, Argentina
Actively Recruiting
23
CHU Helora-Hospital de Mons
Mons, Belgium
Actively Recruiting
24
Hospital de Cancer de Barretos - Fundacao Pio XII
Barretos, Brazil
Actively Recruiting
25
Centro de Pesquisas Clinica Reichow
Blumenau, Brazil
Actively Recruiting
26
CIONC-Centro Integrado de Oncologia de Curitiba
Curitiba, Brazil
Actively Recruiting
27
CRIO - Centro Regional Integrado de Oncologia
Fortaleza, Brazil
Actively Recruiting
28
Liga Norte-Rio-Grandense Contra o Câncer
Natal, Brazil
Actively Recruiting
29
Hospital Ernesto Dornelles
Porto Alegre, Brazil
Actively Recruiting
30
Hospital São Lucas da PUCRS
Porto Alegre, Brazil
Actively Recruiting
31
Centro de Tratamento Oncologico (CTO)
Ribeirão Preto, Brazil
Actively Recruiting
32
Hospital das Clínicas FMRP-USP
Ribeirão Preto, Brazil
Actively Recruiting
33
Obras Sociais Irmã Dulce - Hospital Santo Antônio
Salvador, Brazil
Actively Recruiting
34
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André, Brazil
Actively Recruiting
35
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
Sao Jose Rio Preto, Brazil
Actively Recruiting
36
Centro Paulista de Oncologia S A
Vila Olímpia, Brazil
Actively Recruiting
37
China-Japan Friendship hospital
Beijing, China
Actively Recruiting
38
The First Hospital of Jilin University
Changchun, China
Actively Recruiting
39
Sichuan Cancer Hospital
Chengdu, China
Actively Recruiting
40
West China Hospital, Sichuan University
Chengdu, China
Actively Recruiting
41
Chongqing University Cancer Hospital
Chongqing, China
Actively Recruiting
42
Nanfang Hospital of Southern Medical University
Guangzhou, China
Actively Recruiting
43
Sir Run Run Shaw Hospital of Zhejiang University School of Medicine
Hangzhou, China
Actively Recruiting
44
Harbin Medical University Cancer Hospital
Harbin, China
Actively Recruiting
45
The Second Hospital of Anhui Medical University
Hefei, China
Actively Recruiting
46
Hong Kong Integrated Oncology Centre
Hong Kong, China
Actively Recruiting
47
Cancer Hospital of Shandong First Medical University
Jinan, China
Actively Recruiting
48
Hong Kong United Oncology Centre
Jordan, China
Actively Recruiting
49
Linyi Cancer Hospital
Linyi, China
Actively Recruiting
50
The First Affiliated Hospital of Nanchang University
Nanchang, China
Actively Recruiting
51
The Second Affiliated Hospital of Nanchang University
Nanchang, China
Actively Recruiting
52
Jiangsu Province Hospital
Nanjing, China
Actively Recruiting
53
The Second People's Hospital of Neijiang
Neijiang, China
Actively Recruiting
54
Shanghai East Hospital
Shanghai, China
Actively Recruiting
55
Liaoning Cancer Hospital & Institute
Shenyang, China
Actively Recruiting
56
Shanxi Provincial Cancer Hospital
Taiyuan, China
Actively Recruiting
57
Tianjin Medical University General Hospital
Tianjin, China
Actively Recruiting
58
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China
Actively Recruiting
59
Xiangyang Central Hospital
Xiangyang, China
Actively Recruiting
60
Hopital Albert Calmette - CHU Lille
Lille, France
Actively Recruiting
61
Saitama Medical University International Medical Center
Hidaka-shi, Japan
Actively Recruiting
62
Kansai Medical University Hospital
Hirakata-shi, Japan
Actively Recruiting
63
Hirosaki University Hospital
Hirosaki-shi, Japan
Actively Recruiting
64
St. Marianna University Hospital
Kawasaki-shi, Japan
Actively Recruiting
65
Hospital of the University of Occupational and Environmental Health
Kitakyushu-shi, Japan
Actively Recruiting
66
Saiseikai Kumamoto Hospital
Kumamoto, Japan
Actively Recruiting
67
Kurume University Hospital
Kurume-shi, Japan
Actively Recruiting
68
Matsusaka Municipal Hospital
Matsusaka-shi, Japan
Actively Recruiting
69
NHO Okayama Medical Center
Okayama, Japan
Actively Recruiting
70
Osaka City General Hospital
Osaka, Japan
Actively Recruiting
71
Osaka International Cancer Institute
Osaka, Japan
Actively Recruiting
72
NHO Kinki-Chuo Chest Medical Center
Sakaishi, Japan
Actively Recruiting
73
Keijinkai Teine Keijinkai Hospital
Sapporo, Japan
Actively Recruiting
74
Tokyo Medical University Hospital
Shinjuku-ku, Japan
Actively Recruiting
75
Shizuoka Cancer Center
Sunto-gun, Japan
Actively Recruiting
76
Fujita Health University Hospital
Toyoake-shi, Japan
Actively Recruiting
77
Wakayama Medical University Hospital
Wakayama, Japan
Actively Recruiting
78
Kanagawa Cancer Center
Yokohama, Japan
Actively Recruiting
79
Tottori University Hospital
Yonago-shi, Japan
Actively Recruiting
80
Hospital Kuala Lumpur
Kuala Lumpur, Malaysia
Actively Recruiting
81
Hospital Tengku Ampuan Afzan
Kuantan, Malaysia
Actively Recruiting
82
Beacon Hospital Sdn Bhd
Petaling Jaya, Malaysia
Actively Recruiting
83
Unidade Local de Saude de Santa Maria, E.P.E. - Hospital Pulido Valente
Lisbon, Portugal
Actively Recruiting
84
National Cancer Center
Goyang-si, South Korea
Actively Recruiting
85
Gyeongsang National University Hospital
Jinju, South Korea
Actively Recruiting
86
CHA Bundang Medical Center, CHA University
Seongnam, South Korea
Actively Recruiting
87
Seoul National University Bundang Hospital
Seongnam, South Korea
Actively Recruiting
88
Asan Medical Center
Seoul, South Korea
Actively Recruiting
89
Samsung Medical Center
Seoul, South Korea
Actively Recruiting
90
Severance Hospital, Yonsei University Health System
Seoul, South Korea
Actively Recruiting
91
The Catholic University of Korea, St. Vincent's Hospital
Suwon, South Korea
Actively Recruiting
92
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Taiwan
Actively Recruiting
93
Taichung Veterans General Hospital
Taichung, Taiwan
Actively Recruiting
94
Chi Mei Hospital, Liouying
Tainan, Taiwan
Actively Recruiting
95
National Cheng Kung University Hospital
Tainan, Taiwan
Actively Recruiting
96
Koo Foundation Sun Yat-Sen Cancer Center
Taipei, Taiwan
Actively Recruiting
97
Taipei Veterans General Hospital
Taipei, Taiwan
Actively Recruiting
98
Tri-Service General Hospital
Taipei, Taiwan
Actively Recruiting
99
Chang Gung Memorial Hospital,Linkou
Taoyuan City, Taiwan
Actively Recruiting
100
Charing Cross Hospital
London, United Kingdom
Actively Recruiting
Research Team
C
Contact for Trial Information
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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