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

Metastatic Non Small Cell Lung Cancer Clinical Trial

— TROPION-Lung08  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05215340
• Other study ID #: DS1062-A-U304
• Secondary ID: 2021-002555-10KE
• Status: Recruiting
• Phase: Phase 3
• Start date: March 4, 2022
• Est. completion date: April 30, 2028

Study information

• Verified date: May 2024
• Source: Daiichi Sankyo
• Contact: (US Sites) Daiichi Sankyo Contact for Clinical Trial Information
• Phone: 908-992-6400
• Email: CTRinfo[@]dsi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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) or Overall Survival (OS) for participants with advanced or metastatic NSCLC 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 740
• Est. completion date: April 30, 2028
• Est. primary completion date: February 29, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 NSCLC that meets all of the following criteria:

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 based on analysis of tumor tissue.

3. No known actionable genomic alterations 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.

• 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 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 msec 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Non Small Cell Lung Cancer

Intervention

Drug:
• Datopotamab Deruxtecan
Dato-DXd will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
• Pembrolizumab
Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Argentina	Fundacion CENIT para la investigación en Neurociencias	Ciudad Autonoma de Buenos Aire
Argentina	Hospital Privado de la Comunidad	Mar del Plata
Argentina	Centro de Investigación Pergamino S. A.	Pergamino
Argentina	Instituto de Oncología de Rosario	Rosario
Argentina	Sanatorio Británico de Rosario	Rosario
Argentina	Sanatorio Parque	Rosario
Argentina	CER SAN JUAN - Centro Polivalente de Asistencia e Investigación Clínica	San Juan
Argentina	Clinica Viedma SA	Viedma
Australia	Chris Obrien Lifehouse	Camperdown
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Peninsula and South Eastern Haematology and Oncology Group	Mount Waverley	Victoria
Australia	The Queen Elizabeth Hospital	Woodville South
Austria	Klinikum Klagenfurt am Wörthersee Abteilung für Lungenkrankheiten	Klagenfurt
Austria	Karl-Landsteiner Institute for Lung Research and Pulmonary Oncology c/o Klinik Floridsdorf	Vienna
Belgium	Onze-Lieve-Vrouwziekenhuis Olvz - Campus Aalst	Aalst
Belgium	Grand Hopital de Charleroi - Hopital Saint Joseph	Charleroi
Belgium	Az Maria Middelares - Campus Maria Middelares	Gent
Belgium	AZ Nikolaas	Sint-Niklaas
Brazil	Instituto de Pesquisas em Saúde - IPS	Caxias Do Sul
Brazil	Hospital Erasto Gaertner	Curitiba
Brazil	Oncosite - Centro de Pesquisa Clinica Oncologia	Ijui
Brazil	Clínica de Neoplasias Litoral	Itajaí
Brazil	UPCO - Unidade de Pesquisas Clínicas em Oncologia - Clinica Lacks	Pelotas
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Instituto Nacional de Câncer - INCA	Rio De Janeiro
Brazil	Centro de Estudos e Pesquisa de Hematologia e Oncologia - CEPHO	Santo Andre
Brazil	Instituto de Ensino e Pesquisas Sao Lucas	Sao Paulo
Canada	McGill University Health Centre	Montreal
Canada	Santa Cabrini Hospital	Montréal
Chile	Fundación Arturo Pérez López	Santiago
Chile	Oncovida	Santiago
Chile	Orlandi Oncología	Santiago
Chile	Centro de Estudios Clínicos SAGA	Santiago de Chile	Metropolitana
Chile	Centro de Investigaciones Clinicas Vina Del Mar	Vina Del Mar
China	Peking University Cancer Hospital	Beijing
China	Peking University Peoples Hospital	Beijing
China	Cangzhou People's Hospital	Cangzhou
China	Jilin Cancer Hospital	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha
China	Sichuan Cancer Hospital	Chengdu	Sichuan
China	Army Medical Center of PLA	Chongqing
China	Affiliated Cancer Hospital and Institute of Guangzhou Medical University	Guangzhou
China	Haikou People's Hospital	Haikou
China	The First Affiliated Hospital of College of Medicine Zhejiang University	Hanghzou
China	Zhejiang Cancer Hospital	Hangzhou
China	Harbin Medical University Cancer Hospital	Harbin
China	Inner Mongolia Medical University- the Affiliated Hospital	Hohhot
China	Jiamusi Tumor and Tuberculosis Hospital	Jiamusi
China	Yunnan Cancer Hospital	Kunming
China	Linyi Cancer Hospital	Linyi
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	Jiangsu Province Hospital	Nanjing
China	Guangxi Medical University Affiliated Tumor Hospital	Nanning	Guangxi
China	The Second People's Hospital of Neijiang	Neijiang
China	Shanghai Pulmonary Hospital	Shanghai
China	Fudan University Shanghai Cancer Center	Shanghai Shi
China	The First Hospital of China Medical University	Shenyang
China	Liaoning Cancer Hospital& Institute	Shenyang City
China	Tianjin Medical University General Hospital	Tianjin
China	Xinjiang Tumor Hospital	Ürümqi
China	Hubei Cancer Hospital	Wuhan
China	Union Hospital Affiliated With Tongji Medical College Huazhong University of Science and Technology	Wuhan
China	The First Affiliate Hospitalof Xi'An Jiaotong University	Xi'an
China	The First Affiliated Hospital Xiamen University	Xiamen
China	Xiangyang Central Hospital- 5 Lumen Avenue	Xiangyang
China	Henan Cancer Hospital	Zhengzhou	Henan
France	Bordeaux University Hospital - Hopital Saint Andre	Bordeaux
France	Institut Bergonie	Bordeaux
France	Centre Hospitalier Universitaire de Lille	Lille
France	Centre Leon Berard	Lyon
France	APHM - Hopital Nord	Marseille
France	Centre Hospitalier Universitaire de Montpellier	Montpellier
France	CHU de Nantes	Nantes
France	Hopital prive du Confluent	Nantes Cedex 2
France	AP-HP - Hopital Tenon	Paris
France	CHU de Poitier Pole Regional de Cancerologie	Poitiers
France	Hopital FOCH	Suresnes
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	Klinikum Esslingen GmbH	Esslingen
Germany	LungenClinic Grosshansdorf	Grosshansdorf
Germany	Klinikum der Universitaet Muenchen	Muenchen
Greece	Sotiria General Hosptial of Chest Diseases	Athens
Greece	University Hospital of Ioannina Uhi	Ioannina
Greece	Metropolitan Hospital	Neo Faliro
Greece	Metropolitan Hospital	Neo Faliro	Athens
Greece	Bioclinic Thessaloniki	Thessaloniki
Hong Kong	Prince of Wales Hospital / The Chinese University of Hong Kong 99999	Hong Kong
Hong Kong	Queen Elizabeth Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Pok Fu Lam
Hungary	Semmelweis University Department of Pulmonology	Budapest
Hungary	Veszprem Megyei Tudogyogyintezet Farkasgyepu	Farkasgyepu
Hungary	Bkmk Hospital	KecskemAŠt
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz	Szekesfehervar
Hungary	Pulmonology Hospital Torokbalint	Torokbalint
Italy	IRCCS Istituto Oncologico Giovanni Paolo II	Bari
Italy	UOC Oncologia	Chieti
Italy	Irccs Istituto Europeo Di Oncologia	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliera dei Colli	Naples
Italy	A.O. Perugia Santa Maria della Misericordia	Perugia
Italy	Ifo Regina Elena	Rome
Italy	Policlinico Tor Vergata	Rome
Italy	Asst Sette Laghi Ospedale di Circolo e Fondazione Macchi	Varese
Japan	Aomori Prefectural Central Hospital	Aomori-shi	Aomori
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital	Bunkyo-Ku	Tokyo
Japan	Kyushu University Hospital	Fukuoka-shi	Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka-shi	Fukuoka
Japan	Kansai Medical University Hospital	Hirakata-shi	Osaka
Japan	Saitama Cancer Center	Ina-machi	Saitama
Japan	NHO Iwakuni Clinical Center	Iwakuni-shi	Yamaguchi
Japan	Kanazawa University Hospital	Kanazawa-shi	Ishikawa
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba
Japan	Yamanashi Prefectural Central Hospital	Kofu-shi
Japan	The Cancer Institute Hospital of JFCR	Koto-ku	Toyko
Japan	Saiseikai Kumamoto Hospital	Kumamoto-shi	Kumamoto
Japan	Kurume University Hospital	Kurume-shi	Fukuoka
Japan	University Hospital Kyoto Prefectural University of Medicine	Kyoto-shi
Japan	Matsusaka Municipal Hospital	Matsusaka-shi	Mie
Japan	NHO Shikoku Cancer Center	Matsuyama-shi	Ehime
Japan	Niigata Cancer Center Hospital	Niigata-shi	Niigata
Japan	Osaka Toneyama Medical Center	Osaka
Japan	Osaka International Cancer Institute	Osaka-shi	Osaka
Japan	Toho University Omori Medical Center	Ota-ku	Toyko
Japan	NHO Kinki-Chuo Chest Medical Center	Sakai-shi	Osaka
Japan	Teine Keijinkai Hospital	Sapporo
Japan	Sendai Kousei Hospital	Sendai-shi	Miyagi
Japan	Dokkyo Medical University Hospital	Shimotsuga-gun	Tochigi
Japan	Yamaguchi-Ube Medical Center	Ube-shi	Yamaguchi
Japan	Kanagawa Cancer Center	Yokohama-shi	Kanagawa
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungbuk
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Gyeongsang National University Hospital	Jinju-si	Gyeongsangnam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	The Catholic Univ. of Korea, Seoul St. Mary'S Hospital	Seoul
Korea, Republic of	Asan Medical Center	Songpa-gu
Mexico	Cryptex Investigacion Clinica Sa de Cv	Cuauhtémoc
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey
Mexico	Centro de Investigacion Clinica de Oaxaca (CICLO)	Oaxaca de Juarez
Mexico	Oncologico Potosino	San Luis Potosí
Netherlands	Amsterdam Umc, Location Vumc	Amsterdam
Netherlands	Rijnstate Ziekenhuis	Arnhem	Gelderland
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Jeroen Bosch Ziekenhuis J BZ Hieronymus Bosch Hospital	s-Hertogenbosch
Poland	II Klinika Chorob Pluc I Gruzlicy	Bialystok
Poland	Szpitale Pomorskie Sp. z o.o.	Gdynia	Pomorskie
Poland	Instytut Centrum Zdrowia Matki Polki	Lodz	Iodzkie
Poland	MS Pneumed Janusz Milanowski, Katarzyna Szmygin-Milanowska Sp. Jawna	Lublin
Poland	Dom Lekarski SA	Szczecin	Zachodniopomorskie
Portugal	Centro Clinico Champalimau	Lisboa
Portugal	Centro Hospitalar e Universitário do Porto	Porto
Portugal	Centro Hospitalar Universitário de São João	Porto
Portugal	Hospital CUF Porto	Porto
Portugal	Instituto Portuguas de Oncologia do Porto Francisco Gentil	Porto
Romania	Onco Clinic Consult SA	Craiova
Romania	Sc Sigmedical Services Srl	Suceava
Romania	Oncocenter-Oncologie Clinica SRL	Timisoara
Romania	SC Oncomed SRL	Timisoara
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Hospital Universitario Arnau de Vilanova - Lleida	Lleida
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Regional Universitario Malaga	Malaga
Spain	CHUO	Ourense
Spain	Hospital Universitario de Valme	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Switzerland	Kantonsspital Baden	Baden
Switzerland	University Hospital Basel	Basel
Switzerland	Kantonsspital Baselland	Liestal
Taiwan	Chang Gung Memorial Hospital Cgmh - Kaohsiung Branch	Kaohsiung
Taiwan	E-Da Hospital	Kaohsiung City
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital Nckuh	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital LinKou	Taoyuan
Thailand	Faculty of Medicine Chulalongkorn University	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Prince of Songkla University PSU - Faculty of Medicine	Hat Yai	Songkhla
Thailand	Srinagarind Hospital	Muaeng	Khon Kaen
Turkey	Adana Acibadem Hospital	Adana
Turkey	Ege University	Bornova-Izmir
Turkey	Goztepe Prof. Dr. Suleyman Yalcin City Hospital	Istanbul
Turkey	Medical Park Seyhan Hospital	Seyhan /Adana
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Nottingham University Hospitals	Nottingham
United States	Johns Hopkins University	Baltimore	Maryland
United States	American Oncology Partners of Maryland	Bethesda	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	DFCI - Steward St. Elizabeth's Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Ironwood Cancer and Research Center	Chandler	Arizona
United States	Uch-Mhs D/B/A Memorial Health System	Colorado Springs	Colorado
United States	Astera Cancer Care	East Brunswick	New Jersey
United States	Dana Farber Cancer Institute - Foxborough	Foxboro	Massachusetts
United States	Regional Cancer Care Associates LLC	Freehold	New Jersey
United States	Arizona Oncology NAHOA	Irving	Texas
United States	Cancer Care Center of Brevard	Irving	Texas
United States	Illinois Cancer Specialists	Irving	Texas
United States	Maryland Oncology Hematology	Irving	Texas
United States	Southern Cancer Center	Irving	Texas
United States	Texas Oncology - Northeast Texas	Irving	Texas
United States	Texas Oncology Gulf Coast	Irving	Texas
United States	Texas Oncology McAllen	Irving	Texas
United States	Woodlands Medical	Irving	Texas
United States	Providence Regional Cancer System	Lacey	Washington
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	UCLA HemOnc - Clinical Research Unit	Los Angeles	California
United States	Dana Farber Cancer Institute - Milford Medical Center	Milford	Massachusetts
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Cooperman Barnabas Medical Center	New Brunswick	New Jersey
United States	The Valley Hospital	Paramus	New Jersey
United States	Compassionate Cancer Care Medical Group	Riverside	California
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	University of Texas Health Science Center San Antonio	San Antonio	Texas
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Ridley-Tree Cancer Center	Santa Barbara	California
United States	DFCI - South Shore Hospital	South Weymouth	Massachusetts
United States	PIH Health Whittier Hospital	Whittier	California
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (3)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca, Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Portugal,  Romania,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival Based on Blinded Independent Central Review in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 32 months
Primary	Overall Survival in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 53 months
Secondary	Objective Response Rate by Blinded Independent Central Review in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 per RECIST Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 32 months
Secondary	Progression-free Survival by Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 32 months
Secondary	Progression-free Survival 2 in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	Progression-free Survival 2 (PFS2) 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 local standard clinical practice.	From randomization until disease progression or death (whichever occurs first), up to approximately 53 months
Secondary	Objective Response Rate by Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 the Investigator per RECIST Version 1.1.	From randomization until disease progression or death (whichever occurs first), up to approximately 32 months
Secondary	Duration of Response by BICR and Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 32 months
Secondary	Time to Response by BICR and Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 32 months
Secondary	Disease Control Rate by BICR and Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 32 months
Secondary	Time to Deterioration in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 approximately 53 months
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAE) Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab	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 53 months
Secondary	Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA	The immunogenicity of Dato-DXd in combination with pembrolizumab will be assessed.	Baseline and up to 53 months