Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (TROPION-Lung08)

May 11, 2026 updated by: Daiichi Sankyo

A Randomized, Open-label, Phase 3 Trial of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in Treatment-naïve Subjects With Advanced or Metastatic PD-L1 High (TPS ≥50%) Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung08)

This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab alone in participants with advanced or metastatic non-small cell lung cancer (NSCLC) of non-squamous histology.

Study Overview

Status

Recruiting

Conditions

Metastatic Non Small Cell Lung Cancer

Intervention / Treatment

Detailed Description

The primary objective of the study is to compare the efficacy of Dato-DXd and pembrolizumab with pembrolizumab alone in terms of either Progression Free Survival (PFS) by BICR or Overall Survival (OS) for participants with advanced or metastatic NSCLC with non-squamous histology without actionable genomic alterations whose tumor has high programmed death-ligand 1 (PD-L1) expression (tumor proportion score; TPS ≥50%) and who have not previously received systemic therapy for advanced or metastatic NSCLC.

Eligible participants will be randomized in a 1:1 ratio to the control arm (pembrolizumab alone) or the experimental arm (Dato-DXd and pembrolizumab). The study will be divided into 4 periods: Tissue Screening Period, Screening Period, Treatment Period, and Follow-up Period.

Study Type

Interventional

Enrollment (Estimated)

740

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: (US Sites) Daiichi Sankyo Contact for Clinical Trial Information
Phone Number: 908-992-6400
Email: CTRinfo@dsi.com

Study Contact Backup

Name: (Asia Sites) Daiichi Sankyo Contact for Clinical Trial Informat
Phone Number: +81-3-6225-1111(M-F 9-5 JST)
Email: dsclinicaltrial@daiichisankyo.co.jp

Study Locations

Argentina
- - Buenos Aires, Argentina
    - Recruiting
    - Centro de Investigaciones Médicas y Desarrollo LC S.R.L. (LC Investigación)
  - Ciudad Autonoma de Buenos Aire, Argentina, 1125
    - Recruiting
    - Fundación CENIT para la Investigación en Neurociencias
    - Contact:
      
      Principal Investigator
  - Mar del Plata, Argentina, B7602CBM
    - Recruiting
    - Hospital Privado de la Comunidad
  - Pergamino, Argentina, 2700
    - Recruiting
    - Centro de Investigación Pergamino S. A.
    - Contact:
      
      Principal Investigator
  - Rosario, Argentina, S2000
    - Recruiting
    - Instituto de Oncología de Rosario
    - Contact:
      
      Principal Investigator
  - Rosario, Argentina, S2001
    - Recruiting
    - Sanatorio Parque
    - Contact:
      
      Principal Investigator
  - Rosario, Argentina, S2002
    - Recruiting
    - Sanatorio Britanico de Rosario
    - Contact:
      
      Principal Investigator
  - San Juan, Argentina, 5400
    - Recruiting
    - CER SAN JUAN - Centro Polivalente de Asistencia e Investigación Clínica
  - Viedma, Argentina, 8500
    - Recruiting
    - Clinica Viedma SA
    - Contact:
      
      Principal Investigator
Australia
- - Camperdown, Australia, 2050
    - Recruiting
    - Chris OBrien Lifehouse
    - Contact:
      
      Principal Investigator
  - Woodville South, Australia, 5011
    - Recruiting
    - The Queen Elizabeth Hospital
    - Contact:
      
      Principal Investigator
- Victoria
  - Heidelberg, Victoria, Australia, 3084
    - Recruiting
    - Austin Hospital
    - Contact:
      
      Principal Investigator
  - Mount Waverley, Victoria, Australia, 3149
    - Recruiting
    - Peninsula and South Eastern Haematology and Oncology Group
Austria
- - Klagenfurt, Austria
    - Recruiting
    - Klinikum Klagenfurt am Wörthersee Abteilung für Lungenkrankheiten
  - Vienna, Austria, 1090
    - Recruiting
    - Karl-Landsteiner Institute for Lung Research and Pulmonary Oncology c/o Klinik Floridsdorf
Belgium
- - Aalst, Belgium, 9300
    - Recruiting
    - Onze-Lieve-Vrouwziekenhuis Olvz - Campus Aalst
    - Contact:
      
      Principal Investigator
  - Charleroi, Belgium, 6000
    - Recruiting
    - Grand Hopital de Charleroi - Hopital Saint Joseph
    - Contact:
      
      Principal Investigator
  - Ghent, Belgium, 9000
    - Recruiting
    - Az Maria Middelares - Campus Maria Middelares
    - Contact:
      
      Principal Investigator
  - Sint-Niklaas, Belgium, 9100
    - Recruiting
    - AZ Nikolaas
    - Contact:
      
      Principal Investigator
Brazil
- - Caxias do Sul, Brazil, 95020-972
    - Recruiting
    - Instituto de Pesquisas em Saúde - IPS
    - Contact:
      
      Principal Investigator
  - Curitiba, Brazil, 81520-060
    - Recruiting
    - Hospital Erasto Gaertner
  - Ijuí, Brazil, 98700-000
    - Recruiting
    - Oncosite - Centro de Pesquisa Clinica Oncologia
    - Contact:
      
      Principal Investigator
  - Itajaí, Brazil, 88301-220
    - Recruiting
    - Clinica de Neoplasias Litoral
  - Pelotas, Brazil, 96020-080
    - Recruiting
    - UPCO - Unidade de Pesquisas Clínicas em Oncologia - Clinica Lacks
    - Contact:
      
      Principal Investigator
  - Porto Alegre, Brazil, 90050-170
    - Recruiting
    - Santa Casa de Misericordia de Porto Alegre
    - Contact:
      
      Principal Investigator
  - Rio de Janeiro, Brazil, 20231-050
    - Recruiting
    - Instituto Nacional de Cancer - INCa
    - Contact:
      
      Principal Investigator
  - Santo André, Brazil, 09060-870
    - Recruiting
    - Centro de Estudos e Pesquisa de Hematologia e Oncologia - CEPHO
    - Contact:
      
      Principal Investigator
  - São Paulo, Brazil, 01236-030
    - Recruiting
    - Instituto de Ensino e Pesquisas Sao Lucas
    - Contact:
      
      Principal Investigator
  - Taubaté, Brazil
    - Recruiting
    - Instituto do Cancer Brasil - Unidade Taubate
Canada
- - Montreal, Canada, H4A 3J2
    - Recruiting
    - McGill University Health Centre
  - Montreal, Canada, H1T 2M4
    - Withdrawn
    - Santa Cabrini Hospital
Chile
- - Santiago, Chile, 7500000
    - Recruiting
    - Oncovida
    - Contact:
      
      Principal Investigator
  - Santiago, Chile, 7500921
    - Recruiting
    - Fundación Arturo Pérez López
    - Contact:
      
      Principal Investigator
  - Santiago, Chile, 7501010
    - Recruiting
    - Orlandi Oncologia
  - Viña del Mar, Chile, 254-0488
    - Recruiting
    - Centro de Investigaciones Clinicas Viña del Mar
    - Contact:
      
      Principal Investigator
- Santiago Metropolitan
  - Santiago, Santiago Metropolitan, Chile, 7500653
    - Recruiting
    - Centro de Estudios Clínicos SAGA
    - Contact:
      
      Principal Investigator
China
- - Beijing, China, 100142
    - Recruiting
    - Peking University Cancer Hospital
    - Contact:
      
      Principal Investigator
  - Beijing, China, 100044
    - Recruiting
    - Peking University Peoples Hospital
    - Contact:
      
      Principal Investigator
  - Cangzhou, China, 610001
    - Recruiting
    - Cangzhou People's Hospital
  - Changsha, China, 410013
    - Recruiting
    - Hunan Cancer Hospital
    - Contact:
      
      Principal Investigator
  - Chongqing, China, 400042
    - Recruiting
    - Army Medical Center of PLA
  - Guangzhou, China, 510095
    - Recruiting
    - Affiliated Cancer Hospital and institute of Guangzhou Medical University
    - Contact:
      
      Principal Investigator
  - Haikou, China, 570208
    - Recruiting
    - Haikou People's Hospital
    - Contact:
      
      Principal Investigator
  - Hanghzou, China, 310003
    - Recruiting
    - The First Affiliated Hospital of College of Medicine Zhejiang University
    - Contact:
      
      Principal Investigator
  - Hangzhou, China, 310022
    - Withdrawn
    - Zhejiang Cancer Hospital
  - Harbin, China, 150081
    - Recruiting
    - Harbin medical university cancer hospital
    - Contact:
      
      Principal Investigator
  - Hohhot, China, 10050
    - Recruiting
    - Inner Mongolia Medical University- the Affiliated Hospital
    - Contact:
      
      Principal Investigator
  - Jiamusi, China, 154007
    - Recruiting
    - Jiamusi Tumor and Tuberculosis Hospital
    - Contact:
      
      Principal Investigator
  - Kunming, China, 650118
    - Terminated
    - Yunnan Cancer Hospital
  - Linyi, China, 276000
    - Recruiting
    - Linyi Cancer Hospital
    - Contact:
      
      Principal Investigator
  - Nanchang, China, 330006
    - Recruiting
    - The First Affiliated Hospital of NanChang University
    - Contact:
      
      Principal Investigator
  - Nanjing, China, 210029
    - Recruiting
    - Jiangsu Province Hospital
    - Contact:
      
      Principal Investigator
  - Neijiang, China, 641000
    - Recruiting
    - The Second People's Hospital of Neijiang
    - Contact:
      
      Principal Investigator
  - Shanghai, China, 200433
    - Recruiting
    - Shanghai Pulmonary Hospital
    - Contact:
      
      Principal Investigator
  - Shanghai Shi, China, 200032
    - Recruiting
    - Fudan University Shanghai Cancer Center
    - Contact:
      
      Principal Investigator
  - Shenyang, China, 110001
    - Recruiting
    - The First Hospital of China Medical University
    - Contact:
      
      Principal Investigator
  - Shenyang, China, 110801
    - Recruiting
    - Liaoning Cancer Hospital& Institute
    - Contact:
      
      Principal Investigator
  - Tianjin, China, 300052
    - Recruiting
    - Tianjin Medical University General Hospital
  - Wuhan, China, 430079
    - Recruiting
    - Hubei Cancer Hospital
    - Contact:
      
      Principal Investigator
  - Wuhan, China, 430022
    - Recruiting
    - Union Hospital Affiliated With Tongji Medical College Huazhong University of Science and Technology
    - Contact:
      
      Principal Investigator
  - Xi'an, China, 710061
    - Recruiting
    - The First Affiliate Hospitalof Xi'An Jiaotong University
    - Contact:
      
      Principal Investigator
  - Xiamen, China, 361001
    - Recruiting
    - The First Affiliated Hospital Xiamen University
    - Contact:
      
      Principal Investigator
  - Xiangyang, China, 441000
    - Recruiting
    - Xiangyang Central Hospital- 5 Lumen Avenue
  - Ürümqi, China, 830000
    - Recruiting
    - Xinjiang Tumor Hospital
    - Contact:
      
      Principal Investigator
- Guangxi
  - Nanning, Guangxi, China, 530021
    - Recruiting
    - Guangxi Medical University Affiliated Tumor Hospital
    - Contact:
      
      Principal Investigator
- Henan
  - Zhengzhou, Henan, China, 450008
    - Recruiting
    - Henan Cancer Hospital
    - Contact:
      
      Principal Investigator
- Jilin
  - Changchun, Jilin, China, 130012
    - Recruiting
    - Jilin Cancer Hospital
    - Contact:
      
      Principal Investigator
- Sichuan
  - Chengdu, Sichuan, China, 610049
    - Recruiting
    - Sichuan Cancer Hospital
France
- - Avignon, France, 84000
    - Recruiting
    - Sainte-Catherine Institut du Cancer Avignon-Provence (ICAP)
  - Bordeaux, France, 33076
    - Recruiting
    - Institut Bergonie
    - Contact:
      
      Principal Investigator
  - Bordeaux, France, 33075
    - Recruiting
    - Bordeaux University Hospital - Hopital Saint Andre
  - Lille, France, 59000
    - Recruiting
    - Centre Hospitalier Universitaire De Lille
    - Contact:
      
      Principal Investigator
  - Lyon, France, 69008
    - Recruiting
    - Centre Léon Bérard
  - Marseille, France, 13273
    - Recruiting
    - Institut Paoli-Calmettes
  - Marseille, France, 13015
    - Recruiting
    - Aphm - Hopital Nord
    - Contact:
      
      Principal Investigator
  - Montpellier, France, 34295
    - Recruiting
    - Centre Hospitalier Universitaire de Montpellier
    - Contact:
      
      Principal Investigator
  - Nantes, France, 44093
    - Recruiting
    - CHU de Nantes
    - Contact:
      
      Principal Investigator
  - Nantes, France, 44277
    - Recruiting
    - Hôpital Privé du Confluent
    - Contact:
      
      Principal Investigator
  - Paris, France, 75970
    - Recruiting
    - AP-HP - Hopital Tenon
    - Contact:
      
      Principal Investigator
  - Poitiers, France, 86000
    - Recruiting
    - CHU de Poitier Pole Regional de Cancerologie
    - Contact:
      
      Principal Investigator
  - Suresnes, France, 92150
    - Recruiting
    - Hopital Foch
    - Contact:
      
      Principal Investigator
Germany
- - Berlin, Germany, 13125
    - Recruiting
    - Evangelische Lungenklinik Berlin
    - Contact:
      
      Principal Investigator
  - Esslingen am Neckar, Germany, 73730
    - Recruiting
    - Klinikum Esslingen GmbH
    - Contact:
      
      Principal Investigator
  - Großhansdorf, Germany, 22927
    - Recruiting
    - LungenClinic Grosshansdorf
    - Contact:
      
      Principal Investigator
  - München, Germany, 80336
    - Recruiting
    - Klinikum der Universitaet Muenchen
    - Contact:
      
      Principal Investigator
Greece
- - Athens, Greece, 11527
    - Recruiting
    - Sotiria General Hosptial of Chest Diseases
    - Contact:
      
      Principal Investigator
  - Ioannina, Greece, 45500
    - Recruiting
    - University Hospital of Ioannina Uhi
    - Contact:
      
      Principal Investigator
  - Neo Faliro, Greece, 18547
    - Recruiting
    - Metropolitan Hospital
    - Contact:
      
      Principal Investigator
  - Piraeus, Greece, 18547
    - Recruiting
    - Metropolitan Hospital
  - Thessaloniki, Greece, 54622
    - Recruiting
    - Bioclinic Thessaloniki
  - Thessaloniki, Greece, 55236
    - Recruiting
    - St. Luke's Hospital
- Athens
  - Neo Faliro, Athens, Greece, 14564
    - Recruiting
    - Metropolitan Hospital
    - Contact:
      
      Principal Investigator
Hong Kong
- - Hong Kong, Hong Kong
    - Recruiting
    - Queen Elizabeth Hospital
    - Contact:
      
      Principal Investigator
  - Hong Kong, Hong Kong, 99999
    - Recruiting
    - Prince of Wales Hospital / The Chinese University of Hong Kong 99999
  - Pok Fu Lam, Hong Kong, 999077
    - Recruiting
    - Queen Mary Hospital
    - Contact:
      
      Principal Investigator
Hungary
- - Budapest, Hungary, 1083
    - Recruiting
    - Semmelweis University Department of Pulmonology
    - Contact:
      
      Principal Investigator
  - Farkasgyepű, Hungary, 8582
    - Recruiting
    - Veszprem Megyei Tudogyogyintezet Farkasgyepu
    - Contact:
      
      Principal Investigator
  - KecskemĂŠt, Hungary, 6000
    - Recruiting
    - Bkmk Hospital
    - Contact:
      
      Principal Investigator
  - Székesfehérvár, Hungary, 8000
    - Recruiting
    - Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
    - Contact:
      
      Principal Investigator
  - Törökbálint, Hungary, 2045
    - Recruiting
    - Pulmonology Hospital Torokbalint
    - Contact:
      
      Principal Investigator
Italy
- - Bari, Italy, 70124
    - Recruiting
    - IRCCS Istituto Oncologico Giovanni Paolo II
    - Contact:
      
      Principal Investigator
  - Chieti, Italy, 66100
    - Recruiting
    - UOC Oncologia
    - Contact:
      
      Principal Investigator
  - Lucca, Italy, 55100
    - Recruiting
    - Ospedale San Luca
  - Milan, Italy, 20132
    - Recruiting
    - IRCCS Ospedale San Raffaele
    - Contact:
      
      Principal Investigator
  - Milan, Italy, 20141
    - Recruiting
    - IRCCS Istituto Europeo di Oncologia
    - Contact:
      
      Principal Investigator
  - Naples, Italy, 80131
    - Recruiting
    - Azienda Ospedaliera Dei Colli
    - Contact:
      
      Principal Investigator
  - Perugia, Italy, 06132
    - Recruiting
    - A.O. Perugia Santa Maria della Misericordia
    - Contact:
      
      Principal Investigator
  - Rome, Italy, 144
    - Recruiting
    - IFO Regina Elena
    - Contact:
      
      Principal Investigator
  - Rome, Italy, 133
    - Recruiting
    - Policlinico Tor Vergata
    - Contact:
      
      Principal Investigator
  - Varese, Italy, 21100
    - Recruiting
    - Asst Sette Laghi Ospedale di Circolo e Fondazione Macchi
    - Contact:
      
      Principal Investigator
Japan
- - Kofu, Japan
    - Recruiting
    - Yamanashi Prefectural Central Hospital
  - Kyoto, Japan, 602-8566
    - Recruiting
    - University Hospital Kyoto Prefectural University of Medicine
  - Osaka, Japan, 560-8552
    - Recruiting
    - Osaka Toneyama Medical Center
  - Sapporo, Japan, 006-8555
    - Recruiting
    - Teine Keijinkai Hospital
- Aomori
  - Aomori, Aomori, Japan, 030-8553
    - Recruiting
    - Aomori Prefectural Central Hospital
    - Contact:
      
      Principal Investigator
- Chiba
  - Kashiwa-shi, Chiba, Japan, 277-8577
    - Recruiting
    - National Cancer Center Hospital East
    - Contact:
      
      Principal Investigator
- Ehime
  - Matsuyama, Ehime, Japan, 791-0280
    - Recruiting
    - NHO Shikoku Cancer Center
    - Contact:
      
      Principal Investigator
- Fukuoka
  - Fukuoka, Fukuoka, Japan, 812-8582
    - Recruiting
    - Kyushu University Hospital
    - Contact:
      
      Principal Investigator
  - Fukuoka, Fukuoka, Japan, 811-1395
    - Recruiting
    - National Hospital Organization Kyushu Cancer Center
    - Contact:
      
      Principal Investigator
  - Kurume-shi, Fukuoka, Japan, 830-0011
    - Recruiting
    - Kurume University Hospital
    - Contact:
      
      Principal Investigator
- Ishikawa-ken
  - Kanazawa, Ishikawa-ken, Japan, 920-8641
    - Recruiting
    - Kanazawa University Hospital
    - Contact:
      
      Principal Investigator
- Kanagawa
  - Yokohama, Kanagawa, Japan, 241-8515
    - Recruiting
    - Kanagawa Cancer Center
    - Contact:
      
      Principal Investigator
- Kumamoto
  - Kumamoto, Kumamoto, Japan, 861- 4193
    - Recruiting
    - Saiseikai Kumamoto Hospital
    - Contact:
      
      Principal Investigator
- Mie-ken
  - Matsusaka-shi, Mie-ken, Japan, 515-8544
    - Recruiting
    - Matsusaka Municipal Hospital
    - Contact:
      
      Principal Investigator
- Miyagi
  - Sendai, Miyagi, Japan, 980-0873
    - Recruiting
    - Sendai Kousei Hospital
    - Contact:
      
      Principal Investigator
- Niigata
  - Niigata, Niigata, Japan, 961-8566
    - Recruiting
    - Niigata Cancer Center Hospital
    - Contact:
      
      Principal Investigator
- Osaka
  - Hirakata-shi, Osaka, Japan, 573-1191
    - Recruiting
    - Kansai Medical University Hospital
    - Contact:
      
      Principal Investigator
  - Osaka, Osaka, Japan, 541-8567
    - Recruiting
    - Osaka International Cancer Institute
    - Contact:
      
      Principal Investigator
  - Sakai-shi, Osaka, Japan, 591-8555
    - Recruiting
    - NHO Kinki-Chuo Chest Medical Center
    - Contact:
      
      Principal Investigator
- Saitama
  - Ina-machi, Saitama, Japan, 362-0806
    - Withdrawn
    - Saitama Cancer Center
- Tochigi
  - Shimotsuga-gun, Tochigi, Japan, 321-0293
    - Recruiting
    - Dokkyo Medical University Hospital
    - Contact:
      
      Principal Investigator
- Tokyo
  - Bunkyo-ku, Tokyo, Japan, 113-8431
    - Recruiting
    - Juntendo University Hospital
    - Contact:
      
      Principal Investigator
  - Bunkyō-Ku, Tokyo, Japan, 113-8677
    - Recruiting
    - Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
    - Contact:
      
      Principal Investigator
- Toyko
  - Kōtoku, Toyko, Japan, 135-8550
    - Recruiting
    - The Cancer Institute Hospital of JFCR
    - Contact:
      
      Principal Investigator
  - Ōta-ku, Toyko, Japan, 143-8541
    - Recruiting
    - Toho University Omori Medical Center
    - Contact:
      
      Principal Investigator
- Yamaguchi
  - Iwakuni-shi, Yamaguchi, Japan, 740-8510
    - Recruiting
    - NHO Iwakuni Clinical Center
    - Contact:
      
      Principal Investigator
  - Ube-shi, Yamaguchi, Japan, 755-0241
    - Recruiting
    - Yamaguchi-Ube Medical Center
    - Contact:
      
      Principal Investigator
Mexico
- - Cuauhtémoc, Mexico, 06100
    - Recruiting
    - Cryptex Investigacion Clinica Sa de Cv
    - Contact:
      
      Principal Investigator
  - Guadalajara, Mexico, 44280
    - Recruiting
    - Hospital Civil de Guadalajara Fray Antonio Alcalde
    - Contact:
      
      Principal Investigator
  - Monterrey, Mexico, 64460
    - Recruiting
    - Hospital Universitario Dr. Jose Eleuterio González
    - Contact:
      
      Principal Investigator
  - Oaxaca City, Mexico, 68020
    - Recruiting
    - Centro de Investigación Clinica de Oaxaca (CICLO)
    - Contact:
      
      Principal Investigator
  - San Luis Potosí City, Mexico, 78209
    - Recruiting
    - Oncologico Potosino
    - Contact:
      
      Principal Investigator
Netherlands
- - 's-Hertogenbosch, Netherlands, 5223 GZ
    - Recruiting
    - Jeroen Bosch Ziekenhuis J BZ Hieronymus Bosch Hospital
    - Contact:
      
      Principal Investigator
  - Amsterdam, Netherlands, 1081 HZ
    - Recruiting
    - Amsterdam UMC, location VUmc
    - Contact:
      
      Principal Investigator
  - Leiden, Netherlands, 2333 ZA
    - Recruiting
    - Leiden University Medical Center
    - Contact:
      
      Principal Investigator
- Gelderland
  - Arnhem, Gelderland, Netherlands, 6815 AD
    - Recruiting
    - Rijnstate Ziekenhuis
    - Contact:
      
      Principal Investigator
Poland
- - Bialystok, Poland, 15-450
    - Recruiting
    - II Klinika Chorob Pluc i Gruzlicy
    - Contact:
      
      Principal Investigator
  - Lublin, Poland, 20-064
    - Recruiting
    - MS Pneumed Janusz Milanowski, Katarzyna Szmygin-Milanowska Sp. Jawna
- Iodzkie
  - Lodz, Iodzkie, Poland, 93-338
    - Recruiting
    - Instytut Centrum Zdrowia Matki Polki
    - Contact:
      
      Principal Investigator
- Pomeranian Voivodeship
  - Gdynia, Pomeranian Voivodeship, Poland, 81-519
    - Recruiting
    - Szpitale Pomorskie Sp. z o.o.
- West Pomeranian Voivodeship
  - Szczecin, West Pomeranian Voivodeship, Poland, 70-784
    - Recruiting
    - Dom Lekarski SA
    - Contact:
      
      Principal Investigator
Portugal
- - Lisbon, Portugal, 1400-038
    - Recruiting
    - Centro Clinico Champalimau
    - Contact:
      
      Principal Investigator
  - Porto, Portugal, 4200-319
    - Recruiting
    - Centro Hospitalar Universitario de Sao Joao
  - Porto, Portugal, 4100-180
    - Recruiting
    - Hospital Cuf porto
    - Contact:
      
      Principal Investigator
  - Porto, Portugal, 4099-001
    - Recruiting
    - Centro Hospitalar e Universitário do Porto
    - Contact:
      
      Principal Investigator
  - Porto, Portugal, 4200-072
    - Recruiting
    - Instituto Portuguas de Oncologia do Porto Francisco Gentil
Romania
- - Craiova, Romania, 200094
    - Recruiting
    - Onco Clinic Consult SA
  - Craiova, Romania, 200542
    - Recruiting
    - Centrul De Oncologie SF Nectarie S.R.L.
  - Suceava, Romania, 720214
    - Recruiting
    - Sc Sigmedical Services Srl
  - Timișoara, Romania, 300166
    - Recruiting
    - Oncocenter-Oncologie Clinica SRL
  - Timișoara, Romania, 300239
    - Recruiting
    - SC Oncomed SRL
South Korea
- - Daegu, South Korea, 42119
    - Recruiting
    - Kyungpook National University Chilgok Hospital
    - Contact:
      
      Principal Investigator
  - Goyang-si, South Korea, 10408
    - Recruiting
    - National Cancer Center
    - Contact:
      
      Principal Investigator
  - Seoul, South Korea, 6351
    - Recruiting
    - Samsung Medical Center
    - Contact:
      
      Principal Investigator
  - Seoul, South Korea, 6591
    - Terminated
    - The Catholic Univ. of Korea, Seoul St. Mary'S Hospital
  - Songpa-gu, South Korea, 5505
    - Recruiting
    - Asan Medical Center
    - Contact:
      
      Principal Investigator
- Gyeonggi-do
  - Seongnam-si, Gyeonggi-do, South Korea, 13620
    - Recruiting
    - Seoul National University Bundang Hospital
    - Contact:
      
      Principal Investigator
- Gyeongsangnam-do
  - Jinju, Gyeongsangnam-do, South Korea, 52727
    - Recruiting
    - Gyeongsang National University Hospital
- North Chungcheong
  - Cheongju-si, North Chungcheong, South Korea, 28644
    - Recruiting
    - Chungbuk National University Hospital
    - Contact:
      
      Principal Investigator
Spain
- - Barcelona, Spain, 8035
    - Recruiting
    - Hospital Universitari Vall d'Hebron
    - Contact:
      
      Principal Investigator
  - Barcelona, Spain, 08036
    - Recruiting
    - Hospital Clinic i Provincial de Barcelona
    - Contact:
      
      Principal Investigator
  - Lleida, Spain, 25198
    - Recruiting
    - Hospital Universitario Arnau de Vilanova - Lleida
    - Contact:
      
      Principal Investigator
  - Madrid, Spain, 28040
    - Recruiting
    - Hospital Clinico San Carlos
    - Contact:
      
      Principal Investigator
  - Madrid, Spain, 28007
    - Recruiting
    - Hospital General Universitario Gregorio Marañon
    - Contact:
      
      Principal Investigator
  - Madrid, Spain, 28040
    - Recruiting
    - Hospital Universitario Fundacion Jimenez Diaz
    - Contact:
      
      Principal Investigator
  - Málaga, Spain, 29010
    - Recruiting
    - Hospital Regional Universitario Malaga
    - Contact:
      
      Principal Investigator
  - Ourense, Spain, 32005
    - Recruiting
    - CHUO
    - Contact:
      
      Principal Investigator
  - Seville, Spain, 41009
    - Recruiting
    - Hospital Universitario Virgen Macarena
    - Contact:
      
      Principal Investigator
  - Seville, Spain, 41014
    - Recruiting
    - Hospital Universitario de Valme
  - Valencia, Spain, 46026
    - Recruiting
    - Hospital Universitari i Politecnic La Fe
    - Contact:
      
      Principal Investigator
  - Zaragoza, Spain, 50009
    - Recruiting
    - Hospital Universitario Miguel Servet
    - Contact:
      
      Principal Investigator
Switzerland
- - Baden, Switzerland, 5404
    - Recruiting
    - Kantonsspital Baden
    - Contact:
      
      Principal Investigator
  - Basel, Switzerland, 4031
    - Recruiting
    - University Hospital Basel
    - Contact:
      
      Principal Investigator
  - Liestal, Switzerland, A4410
    - Recruiting
    - Kantonsspital Baselland
    - Contact:
      
      Principal Investigator
  - Sankt Gallen, Switzerland
    - Recruiting
    - Kantonsspital St. Gallen
Taiwan
- - Kaohsiung City, Taiwan, 824
    - Recruiting
    - E-DA Hospital
    - Contact:
      
      Principal Investigator
  - Kaohsiung City, Taiwan, 833
    - Recruiting
    - Chang Gung Memorial Hospital CGMH - Kaohsiung Branch
    - Contact:
      
      Principal Investigator
  - Taichung, Taiwan, 40705
    - Recruiting
    - Taichung Veterans General Hospital
    - Contact:
      
      Principal Investigator
  - Taichung, Taiwan, 40201
    - Recruiting
    - Chung Shan Medical University Hospital
    - Contact:
      
      Principal Investigator
  - Tainan, Taiwan, 704
    - Recruiting
    - National Cheng Kung University Hospital NCKUH
    - Contact:
      
      Principal Investigator
  - Taipei, Taiwan, 100
    - Recruiting
    - National Taiwan University Hospital
    - Contact:
      
      Principal Investigator
  - Taipei, Taiwan, 11217
    - Recruiting
    - Taipei Veterans General Hospital
    - Contact:
      
      Principal Investigator
  - Taipei, Taiwan, 112
    - Recruiting
    - Koo Foundation Sun Yat-Sen Cancer Center
    - Contact:
      
      Principal Investigator
  - Taoyuan, Taiwan, 333
    - Recruiting
    - Chang Gung Memorial Hospital LinKou
    - Contact:
      
      Principal Investigator
Thailand
- - Bangkok, Thailand, 10700
    - Recruiting
    - Siriraj Hospital
    - Contact:
      
      Principal Investigator
  - Bangkok, Thailand, 10330
    - Recruiting
    - Faculty of Medicine Chulalongkorn University
    - Contact:
      
      Principal Investigator
- Changwat Khon Kaen
  - Muaeng, Changwat Khon Kaen, Thailand, 40002
    - Recruiting
    - Srinagarind Hospital
    - Contact:
      
      Principal Investigator
- Changwat Songkhla
  - Hat Yai, Changwat Songkhla, Thailand, 90110
    - Recruiting
    - Prince of Songkla University PSU - Faculty of Medicine
    - Contact:
      
      Principal Investigator
Turkey (Türkiye)
- - Adana, Turkey (Türkiye), 1130
    - Recruiting
    - Adana Acibadem Hospital
  - Antalya, Turkey (Türkiye), 7070
    - Recruiting
    - Akdeniz University Hospital
  - Bornova-İzmir, Turkey (Türkiye), 35100
    - Recruiting
    - Ege University
  - Istanbul, Turkey (Türkiye), 34772
    - Recruiting
    - Goztepe Prof. Dr. Suleyman Yalcin City Hospital
  - Seyhan /Adana, Turkey (Türkiye), 1140
    - Recruiting
    - Medical Park Seyhan Hospital
  - Çankaya, Turkey (Türkiye), 06520
    - Recruiting
    - Memorial Ankara Hospital Ankara
United Kingdom
- - Birmingham, United Kingdom, B9 5SS
    - Recruiting
    - Birmingham Heartlands Hospital
    - Contact:
      
      Principal Investigator
  - Glasgow, United Kingdom, G12 0YN
    - Withdrawn
    - Beatson West Of Scotland Cancer Centre
  - Nottingham, United Kingdom, NG5 1PB
    - Recruiting
    - Nottingham University Hospitals
    - Contact:
      
      Principal Investigator
United States
- Arizona
  - Chandler, Arizona, United States, 85224
    - Recruiting
    - Ironwood Cancer and Research Center
    - Contact:
      
      Principal Investigator
- California
  - Los Angeles, California, United States, 90095
    - Recruiting
    - UCLA HemOnc - Clinical Research Unit
  - Riverside, California, United States, 92501
    - Withdrawn
    - Compassionate Cancer Care Medical Group
  - San Francisco, California, United States, 94158
    - Withdrawn
    - UCSF Helen Diller Family Comprehensive Cancer Center
  - Santa Barbara, California, United States, 93105
    - Recruiting
    - Ridley-Tree Cancer Center
  - Whittier, California, United States, 90602
    - Recruiting
    - PIH Health Whittier Hospital
    - Contact:
      
      Principal Investigator
  - Whittier, California, United States, 90603
    - Terminated
    - The Oncology Institute of Hope and Innovation
- Colorado
  - Colorado Springs, Colorado, United States, 80909
    - Recruiting
    - Uch-Mhs D/B/A Memorial Health System
    - Contact:
      
      Principal Investigator
- Maryland
  - Baltimore, Maryland, United States, 21205
    - Recruiting
    - Johns Hopkins University
    - Contact:
      
      Principal Investigator
  - Bethesda, Maryland, United States, 20817
    - Recruiting
    - American Oncology Partners of Maryland
    - Contact:
      
      Principal Investigator
- Massachusetts
  - Boston, Massachusetts, United States, 02215
    - Recruiting
    - Beth Israel Deaconess Medical Center
  - Boston, Massachusetts, United States, 02115
    - Recruiting
    - Dana-Farber Cancer Institute
    - Contact:
      
      Principal Investigator
  - Boston, Massachusetts, United States, 02215
    - Withdrawn
    - DFCI - Steward St. Elizabeth's Medical Center
  - Foxborough, Massachusetts, United States, 02035
    - Terminated
    - Dana Farber Cancer Institute - Foxborough
  - Milford, Massachusetts, United States, 01757
    - Withdrawn
    - Dana Farber Cancer Institute - Milford Medical Center
  - South Weymouth, Massachusetts, United States, 02190
    - Terminated
    - DFCI - South Shore Hospital
- New Hampshire
  - Lebanon, New Hampshire, United States, 03766
    - Recruiting
    - Dartmouth Hitchcock Medical Center
    - Contact:
      
      Principal Investigator
- New Jersey
  - East Brunswick, New Jersey, United States, 08816
    - Recruiting
    - Astera Cancer Care
    - Contact:
      
      Principal Investigator
  - Freehold, New Jersey, United States, 07728
    - Recruiting
    - Regional Cancer Care Associates LLC
    - Contact:
      
      Principal Investigator
  - New Brunswick, New Jersey, United States, 08901
    - Recruiting
    - Cooperman Barnabas Medical Center
    - Contact:
      
      Principal Investigator
  - Paramus, New Jersey, United States, 07652
    - Recruiting
    - The Valley Hospital
    - Contact:
      
      Principal Investigator
- New York
  - The Bronx, New York, United States, 10461
    - Recruiting
    - Montefiore Medical Center
    - Contact:
      
      Principal Investigator
- Texas
  - Irving, Texas, United States, 75063
    - Recruiting
    - Cancer Care Center of Brevard
  - Irving, Texas, United States, 75063
    - Recruiting
    - Maryland Oncology Hematology
  - Irving, Texas, United States, 75063
    - Recruiting
    - Southern Cancer Center
  - Irving, Texas, United States, 75063
    - Recruiting
    - Texas Oncology - Northeast Texas
  - Irving, Texas, United States, 75063
    - Recruiting
    - Texas Oncology Gulf Coast
  - Irving, Texas, United States, 75063
    - Recruiting
    - Texas Oncology McAllen
  - Irving, Texas, United States, 75063
    - Recruiting
    - Illinois Cancer Specialists
  - Irving, Texas, United States, 75063
    - Withdrawn
    - Woodlands Medical
  - Irving, Texas, United States, 75063
    - Terminated
    - Arizona Oncology NAHOA
  - San Antonio, Texas, United States, 78229
    - Recruiting
    - University of Texas Health Science Center San Antonio
    - Contact:
      
      Principal Investigator
- Utah
  - Salt Lake City, Utah, United States, 84106
    - Recruiting
    - Utah Cancer Specialists
    - Contact:
      
      Principal Investigator
- Washington
  - Lacey, Washington, United States, 98503
    - Recruiting
    - Providence Regional Cancer System
    - Contact:
      
      Principal Investigator
  - Seattle, Washington, United States, 98108
    - Recruiting
    - VA Puget Sound Health Care System - VAPSHCS
- Wisconsin
  - Milwaukee, Wisconsin, United States, 53226
    - Terminated
    - Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Description

Inclusion Criteria:

Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.

Sign and date the Tissue Screening and Main Informed Consent Forms, prior to the start of any study-specific qualification procedures.
Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
Histologically documented non-squamous NSCLC that meets all of the following criteria (Note: Subjects with squamous histology were eligible prior to Protocol Version 5.0. After Protocol Version 5.0, subjects with squamous histology are not eligible. Subjects with mixed histology, including those with a squamous component, remain eligible the study even after Protocol Version 5.0):
1. Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC disease at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition). Participants with early-stage NSCLC who have relapsed should be restaged during screening to ensure their eligibility for the study.
2. Documented negative test results for epidermal growth factor receptor (EGFR), lymphoma kinase (ALK), and proto-oncogene1 (ROS1) actionable genomic alterations (AGAs) based on analysis of tumor tissue. If test results for EGFR, ALK, and ROS1 are not available, subjects are required to undergo testing performed locally for these genomic alterations.
3. No known AGAs in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET), mesenchymal-epithelial transition factor (MET), or other actionable driver kinases with locally approved therapies. (Testing for genomic alterations besides EGFR, ALK, and ROS1 is not required prior to randomization). Subjects whose tumors harbor KRAS mutations are eligible for the study.
Has provided a formalin-fixed tumor tissue sample for the measurement of trophoblast cell surface protein 2 (TROP2) protein expression and for the assessment of other exploratory biomarkers.
Tumor has high programmed death receptor-1 (PD-L1) expression (TPS ≥50%) as determined by PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay by central testing (minimum of 6 slides).
Has an adequate treatment washout period before Cycle 1 Day 1.
Measurable disease based on local imaging assessment using RECIST Version 1.1.
Has left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days before randomization.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at screening.
Has a life expectancy of at least 3 months.
Adequate bone marrow function within 7 days before randomization.

Exclusion Criteria:

Has received prior systemic treatment for advanced or metastatic NSCLC.
Has received prior treatment for NSCLC with any of the following, including in the adjuvant/neoadjuvant setting:
1. Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I.
2. TROP2-targeted therapy.
3. Any anti-programmed death receptor-1 (PD-1), anti-PD-L1, or anti-PD-ligand 2 (L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
4. Any other immune checkpoint inhibitors. Participants who received adjuvant or neoadjuvant therapy OTHER than those listed above, are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced/metastatic disease.
Has spinal cord compression or active and untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases and who are asymptomatic may participate provided they are radiologically stable.
Has received prior radiotherapy < 4 weeks of start of study intervention or more than 30 Gy (unit of ionizing radiation dose in the International System of Units) to the lung within 6 months of Cycle 1 Day 1.
History of another primary malignancy (beyond NSCLC) except for:
1. Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study treatment and of low potential risk for recurrence.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
4. Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression and who in the opinion of the Investigator are not deemed to require active intervention.
Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Clinically severe pulmonary compromise, as judged by the investigator, resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement or prior complete pneumonectomy.
Uncontrolled or significant cardiovascular disease, including:
1. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 ms regardless of sex (based on the average of the 12-lead electrocardiogram determination at screening).
2. Myocardial infarction within 6 months prior to randomization.
3. Uncontrolled angina pectoris within 6 months prior to randomization.
4. LVEF <50% by ECHO or MUGA scan within 28 days before randomization.
5. New York Heart Association Class 2 to 4 congestive heart failure (CHF) at screening.
6. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before randomization.

Participants with a history of Class 2 to 4 CHF prior to screening, must have returned to Class 1 CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.

Clinically significant corneal disease.
Has received a live vaccine or live-attenuated vaccine (messenger ribonucleic acid and replication-incompetent adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of study drug. For any participant receiving an approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine, please follow the vaccine label and/or local guidance.
Active, known, or suspected autoimmune disease (has an active autoimmune disease that has required systemic treatment in the past 2 years).
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosage >10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy ≤7 days prior to the first dose of study drug.
Has known human immunodeficiency virus (HIV) infection that is not well controlled.
Has an active hepatitis or uncontrolled hepatitis B or active hepatitis C infection.
Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
Had an allogeneic tissue/solid organ transplant.
Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd or pembrolizumab.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + Datopotamab Deruxtecan (Dato-DXd) Participants will be randomized to receive 200 mg pembrolizumab followed by 6.0mg/kg Dato-DXd.	Drug: Datopotamab Deruxtecan Dato-DXd will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle. Other Names: Dato-DXd Drug: Pembrolizumab Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle. Other Names: KEYTRUDA®
Active Comparator: Pembrolizumb Participants will be randomized to receive 200 mg pembrolizumab.	Drug: Pembrolizumab Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle. Other Names: KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Based on Blinded Independent Central Review in Participants With Non-Squamous Histology Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 44 months	Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 44 months
Overall Survival (OS) in Participants With Non-Squamous Histology Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab Time Frame: From randomization until date of death due to any cause, up to approximately 71 months	Overall Survival (OS) is defined as the time from randomization to death due to any cause.	From randomization until date of death due to any cause, up to approximately 71 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS in All Randomized Participants, Including Participants With Squamous and Non-Squamous Histology Time Frame: From randomization until date of death due to any cause, up to approximately 71 months	Overall Survival (OS) is defined as the time from randomization to death due to any cause.	From randomization until date of death due to any cause, up to approximately 71 months
PFS Based on BICR in All Randomized Participants, Including Participants With Squamous and Non-Squamous Histology Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 44 months	PFS is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 44 months
Progression-free Survival by Investigator in Participants with Non-Squamous Histology, and Separately for All Randomized Participants Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 44 months	Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by the Investigator per RECIST Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 44 months
Progression-free Survival 2 in Participants with Non-Squamous Histology, and Separately for All Randomized Participants Time Frame: From randomization until disease progression on the next line of therapy or death (whichever occurs first), up to approximately 71 months	Progression-free Survival 2 (PFS2) is defined as the time from date of randomization to the first documented disease progression on next-line therapy or death due to any cause, whichever occurs first.	From randomization until disease progression on the next line of therapy or death (whichever occurs first), up to approximately 71 months
ORR by BICR and Investigator in Participants with Non-Squamous Histology, and Separately for All Randomized Participants Time Frame: From randomization to first confirmed response, up to approximately 44 months	Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by BICR and by the Investigator per RECIST Version 1.1.	From randomization to first confirmed response, up to approximately 44 months
Duration of Response by BICR and Investigator in Participants with Non-Squamous Histology, and Separately for All Randomized Participants Time Frame: From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 44 months	Duration of Response (DoR) is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first radiographic disease progression or death due to any cause, whichever occurs first, assessed by BICR and by the Investigator per RECIST Version 1.1.	From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 44 months
Time to Response by BICR and Investigator in Participants with Non-Squamous Histology, and Separately for All Randomized Participants Time Frame: From randomization to date of first objective response (CR or PR), up to approximately 44 months	Time to Response (TTR) is defined as the time from randomization to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding participants, assessed by BICR and by the Investigator per RECIST Version 1.1.	From randomization to date of first objective response (CR or PR), up to approximately 44 months
Disease Control Rate by BICR and Investigator in Participants with Non-Squamous Histology, and Separately for All Randomized Participants Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 44 months	Disease Control Rate (DCR) is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD), assessed by BICR and by the Investigator per RECIST Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 44 months
Time to Deterioration in Participants with Non-Squamous Histology, and Separately for All Randomized Participants Time Frame: From randomization until disease progression or death (whichever occurs first), up to 71 months	Time to Deterioration (TTD) is defined as the time from randomization to first onset of a ≥10-point increase in cough, chest pain, or dyspnea, confirmed by a second adjacent ≥10-point increase from randomization in the same symptom, or confirmed by death within 21 days of a ≥10-point increase from randomization, assessed the European Organization for Research and Treatment of Cancer Lung cancer module (EORTC-QLQ-LC13).	From randomization until disease progression or death (whichever occurs first), up to 71 months
Number of Participants With Treatment-emergent Adverse Events (TEAE) with Non-Squamous Histology, and Separately for All Randomized Participants Time Frame: Up to 71 months	A TEAE is defined as an AE with a start or worsening date on or after the start date of study treatment until 37 days after the end date of study treatment.	Up to 71 months
Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA for Participants with Non-Squamous Histology, and Separately for All Randomized Participants Time Frame: Baseline and up to 71 months	The immunogenicity of Dato-DXd in combination with pembrolizumab will be assessed.	Baseline and up to 71 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daiichi Sankyo

Collaborators

Merck Sharp & Dohme LLC

AstraZeneca

Investigators

Study Director: Global Clinical Leader, Daiichi Sankyo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Levy BP, Felip E, Reck M, Yang JC, Cappuzzo F, Yoneshima Y, Zhou C, Rawat S, Xie J, Basak P, Xu L, Sands J. TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC. Future Oncol. 2023 Jul;19(21):1461-1472. doi: 10.2217/fon-2023-0230. Epub 2023 May 30.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2022

Primary Completion (Estimated)

February 29, 2028

Study Completion (Estimated)

April 30, 2028

Study Registration Dates

First Submitted

January 18, 2022

First Submitted That Met QC Criteria

January 18, 2022

First Posted (Actual)

January 31, 2022

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 11, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

DS1062-A-U304
2021-002555-10 (EudraCT Number)
KEYNOTE-C73 (Other Identifier: Merck)
MK3475-C73 (Other Identifier: Merck)
2023-507933-12-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual participant data (IPD) 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/

IPD Sharing Time Frame

Studies 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.

IPD Sharing Access Criteria

Formal request from qualified scientific and medical researchers on IPD and clinical study documents from 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.

IPD Sharing Supporting Information Type

STUDY_PROTOCOL
SAP
ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Guizhou Medical University

Not yet recruiting

Phase III, Multicenter, Randomized Controlled Clinical Study of Three-Dimensional Radiotherapy for Primary Tumors in Non-Oligometastatic Stage IV Non-Small Cell Lung Cancer

Non Small Cell Lung Cancer Metastatic | Radiotherapy
Genentech, Inc.

Completed

A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors

Non-Small Cell Lung Cancer, Metastatic Colorectal Cancer, Metastatic Non Small Cell Lung Cancer, Metastatic Cancers, Melanoma

United States
Western Regional Medical Center

Terminated

Neoadjuvant Chemo for Non-metastatic Non-small Cell Lung Cancer

Non-squamous Cell Non-Metastatic Non-Small Cell Lung Cancer | Squamous Cell Non-Metastatic Non-Small Cell Lung Cancer

United States
University of California, Davis
National Cancer Institute (NCI)

Recruiting

Risk-adapted, Proteomic-guided Systemic Therapy for Previously Untreated Advanced Non-small Cell Lung Cancer

Non Small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage IV | Non-small Cell Lung Cancer Stage IIIC | Non-small Cell Lung Cancer Unresectable

United States
Genelux Corporation
Newsoara Biopharma Co., Ltd.

Recruiting

Efficacy & Safety of Olvimulogene Nanivacirepvec & Platinum-doublet + Physician's Choice of Immune Checkpoint Inhibitor Compared to Docetaxel in NSCL Cancer (VIRO-25)

Non-small Cell Lung Cancer Stage III | Non-small Cell Lung Cancer | Advanced Non-squamous Non-small-cell Lung Cancer | Non-small Cell Lung Cancer Stage IV | Metastatic Squamous Non-Small Cell Lung Carcinoma | Non-small Cell Lung Cancer Recurrent | Metastatic Non-squamous Non Small Cell Lung Cancer and other conditions

United States
Royal Marsden NHS Foundation Trust
University of Cambridge; Royal Brompton & Harefield NHS Foundation Trust; Institute... and other collaborators

Recruiting

Feasibility Study of Tissue and Blood Collection in Oncogene-addicted and Neoadjuvantly Treated Non Small Cell Lung Cancer (FeStival)

Non Small Cell Lung Cancer | Metastatic Non Small Cell Lung Cancer | Locally Advanced NSCLC - Non-Small Cell Lung Cancer | Oncogene-addicted Non Small Cell Lung Cancer | Early-stage Operable Non Small Cell Lung Cancer | Stage 2/3 Operable Non Small Cell Lung Cancer

United Kingdom
Jiangxi Provincial People's Hopital

Not yet recruiting

Xingbai Ji Formula Combined with Chemotherapy and Sintilimab in Metastatic Multi-Target Mutation-Negative Non-Small Cell Lung Cancer: a Clinical Trial

Non-Small Cell Lung Cancer | Non-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer Stage IIIB | Non-small Cell Lung Cancer Stage IV | Non-small Cell Lung Cancer Recurrent

China

Clinical Trials on Datopotamab Deruxtecan

Medical University of Vienna
Daiichi Sankyo

Recruiting

Phase II Study of Dato-DXd in Triple-negative Breast Cancer Patients With Newly Diagnosed or Progressing Brain Metastases (TUXEDO-2)

Breast Cancer Stage IV

Austria
Daiichi Sankyo
AstraZeneca

Completed

Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)

Non-small Cell Lung Cancer

United States, Spain, Italy, Taiwan, Japan, France, Germany, Hungary, Netherlands, South Korea
AstraZeneca

Recruiting

A Study of AZD3470, a PRMT5 Inhibitor, Given as Monotherapy and in Combination in Patients With MTAP Deficient Advanced/Metastatic Solid Tumors (PRIMROSE)

Advanced Solid Tumors That Are MTAP Deficient

United States, China, Spain, Australia, Japan, Netherlands, France, South Korea
Fundación Pública Andaluza para la Investigación...

Recruiting

Impact of Genetic Variants on the Toxicity of Antibody-Drug Conjugates in Locally Advanced or Metastatic Breast Cancer: The Role of the UGT1A1 Gene as a Predictive Biomarker of Therapeutic Response

Breast Cancer | Metastatic Breast Cancer | Drug-Related Side Effects and Adverse Reactions | Pharmacogenetic Variant

Spain
Daiichi Sankyo
AstraZeneca

Approved for marketing

Medical Access Program for Datopotamab Deruxtecan in EGFRm NSCLC Patients

EGFRm Advanced Non-Small Cell Lung Cancer | EGFRm Metastatic Non-Small Cell Lung Cancer

United States
AstraZeneca
Daiichi Sankyo

Not yet recruiting

An Open-label, Single-arm Study of Prophylaxis for Datopotamab Deruxtecan (Dato-DXd) -Related Stomatitis in Eligible Patients With Metastatic or Inoperable Locally Recurrent Breast Cancer or Locally Advanced or Metastatic Epidermal Growth Factor Receptor-Mutated Non-small Cell Lung Cancer. (TROPION-SWISH)

Stomatitis

United States
UNC Lineberger Comprehensive Cancer Center
AstraZeneca; Translational Breast Cancer Research Consortium

Recruiting

PREDICT-RD: ctDNA Surveillance in TNBC With Residual Disease (PREDICT-RD)

Breast Cancer | Residual Disease | Triple Negative Breast Cancer (TNBC) | Stage II/III

United States
AstraZeneca
Daiichi Sankyo

Active, not recruiting

A Study of Dato-DXd in Chinese Patients With Advanced Non-Small Cell Lung Cancer, Triple-negative Breast Cancer and Other Solid Tumors (TROPION-PanTumor02)

Carcinoma, Non-Small-Cell Lung | Triple Negative Breast Cancer

China
Sarah Sammons, MD
Daiichi Sankyo

Recruiting

DATO-BASE: DATOpotamab-deruxtecan for Breast Cancer Brain metAstaSEs

Breast Cancer | Breast Cancer Female | Metastatic Triple-Negative Breast Carcinoma | HER2-negative Breast Cancer | HER2 Negative Breast Carcinoma | ER-negative Breast Cancer | ER Positive Breast Cancer

United States
Queen Mary University of London
AstraZeneca

Recruiting

Investigating Datopotamab Deruxtecan Plus Durvalumab Versus Datopotamab Deruxtecan in Patients With PDL1-negative Metastatic Triple-negative Breast Cancer (DIAMOND)

Triple Negative Breast Cancer

United Kingdom

Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (TROPION-Lung08)

A Randomized, Open-label, Phase 3 Trial of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in Treatment-naïve Subjects With Advanced or Metastatic PD-L1 High (TPS ≥50%) Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung08)

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