M7824 Versus Pembrolizumab as a First-line (1L) Treatment in Participants With Programmed Death-ligand 1 (PD-L1) Expressing Advanced Non-small Cell Lung Cancer (NSCLC)
An Adaptive Phase III, Multicenter, Randomized, Open-Label, Controlled Study of M7824 (Bintrafusp Alfa) Versus Pembrolizumab as a First-line Treatment in Patients With PD-L1 Expressing Advanced Non-small Cell Lung Cancer
2 other identifiers
interventional
304
18 countries
119
Brief Summary
The purpose of the study is to evaluate the efficacy and safety of bintrafusp alfa (M7824) compared with pembrolizumab in participants with advanced NSCLC with high PD-L1-tumor expression, with no epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation. The Phase III adaptive design allows for the option to recruit up to 584 patients based on pre-specified rules.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3 nonsmall-cell-lung-cancer
Started Oct 2018
Typical duration for phase_3 nonsmall-cell-lung-cancer
119 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 9, 2018
CompletedFirst Posted
Study publicly available on registry
August 15, 2018
CompletedStudy Start
First participant enrolled
October 1, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 7, 2021
CompletedResults Posted
Study results publicly available
June 29, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 25, 2024
CompletedApril 8, 2025
March 1, 2025
2.7 years
August 9, 2018
June 6, 2022
March 21, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
Progression free survival was defined as the time from randomization of study intervention until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days
Overall Survival (OS)
Overall Survival was defined as the time from randomization of study intervention to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method.
Time from randomization of study drug assessed approximately up to 843 days
Secondary Outcomes (3)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
Time from first treatment assessed up to approximately 843 days
Percentage of Participants With Unconfirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
From first documented objective response to PD or death due to any cause, assessed approximately up to 746 days
Study Arms (2)
M7824
EXPERIMENTALPembrolizumab
ACTIVE COMPARATORInterventions
Participants received intravenous infusion of M7824 at a dose of 1200 milligrams (mg) once every 2 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Pembrolizumab: Participants received intravenous infusion of Pembrolizumab at a dose of 200 milligrams (mg) once every 3 weeks until confirmed progression of disease, death, unacceptable toxicity, or study withdrawal.
Eligibility Criteria
You may qualify if:
- Histologically confirmed diagnosis of advanced NSCLC
- Have not received prior systemic therapy treatment for their advanced/Stage four NSCLC. Completion of treatment with cytotoxic chemotherapy, biological therapy, and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease. Confirmation of resolution of toxic effects of previous neoadjuvant/adjuvant chemotherapy therapy to Grade less than or equal to 1. For radiation toxicity or prior major surgeries, participants should have recovered from side effects and/or complications
- Have measurable disease based on RECIST 1.1
- Have a life expectancy of at least 3 months
- Availability of tumor tissue (less than 6 months old) before the first dose is mandatory to determine PD-L1 expression level prior to enrollment
- PD-L1 high status as determined by central testing
You may not qualify if:
- Participants with nonsquamous NSCLC histologies whose tumor harbors any of the following molecular alterations and targeted therapy is locally approved: epidermal growth factor receptor (EGFR) sensitizing (activating) mutation, anaplastic lymphoma kinase (ALK) translocation, ROS1 rearrangement, or BRAF V600E mutation
- Has received major surgery within 4 weeks prior to the first dose of study intervention; received thoracic radiation therapy of greater than 30 units of gray (Gy) within 6 months prior to the first dose of study
- Known severe hypersensitivity to investigational products (M7824 or pembrolizumab), or any components in their formulations
- Previous malignant disease (other than the target malignancy to be investigated in this study) within the last 3 years
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (119)
Oncology Specialties, PC; Clearview Cancer Institute
Huntsville, Alabama, 35805, United States
Cedars Sinai Medical Center - Inflammatory Bowel Disease Center (Clinic
Los Angeles, California, 90048, United States
UC Irvine Medical Center
Orange, California, 92868, United States
Kaiser Permanente - Harbor City
San Diego, California, 92120, United States
Sansum Clinic - Santa Barbara
Santa Barbara, California, 93105, United States
Rocky Mountain Cancer Centers - Colorado Springs, N. Nevada
Colorado Springs, Colorado, 80907, United States
Eastern Connecticut Hematology/Oncology Assoc.
Norwich, Connecticut, 06360, United States
Cancer Specialists, LLC - Department of Clinical Research
Jacksonville, Florida, 32256, United States
Woodlands Medical Specialists
Pensacola, Florida, 32503, United States
The University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Decatur Memorial Hospital - Clinical Research
Decatur, Illinois, 62526, United States
Baptist Health Lexington Oncology Associates
Lexington, Kentucky, 40503, United States
Norton Cancer Institute
Louisville, Kentucky, 40202, United States
Henry Ford Medical Center
Detroit, Michigan, 48202, United States
Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC - Menorah Medical Center - Oncology Account
Kansas City, Missouri, 64132, United States
Southeast Nebraska Cancer Center
Lincoln, Nebraska, 68510, United States
The Valley Hospital - Luckow Pavilion
Paramus, New Jersey, 07652, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
UPMC Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
SCRI - Tennessee Oncology
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Texas Oncology - Bedford
Bedford, Texas, 76022, United States
Texas Oncology, P.A. - Sugarland
Sugar Land, Texas, 77479, United States
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031, United States
Centro de Oncologia e Investigacion Buenos Aires
Berazategui, B1880BBF, Argentina
Instituto Medico Especializado Alexander Fleming
Ciudad Autonoma Buenos Aires, C1426ANZ, Argentina
Sanatorio Allende
Córdoba, X5000JHQ, Argentina
Instituto Medico Rio Cuarto
Río Cuarto, 5800, Argentina
Instituto de Oncología de Rosario
Rosario, S2000KZE, Argentina
Centro Medico San Roque S.R.L.
San Miguel de Tucumán, 4000, Argentina
Universitair Ziekenhuis Brussel - Geriatrie
Brussels, 1090, Belgium
Jessa Ziekenhuis Hospital
Hasselt, 3500, Belgium
UZ Leuven
Pellenberg, 3212, Belgium
CHU Mont-Godinne
Yvoir, 5530, Belgium
Hospital de Câncer de Barretos - Fundação Pio XII
Barretos, 14784-400, Brazil
CRIO - Centro Regional Integrado de Oncologia
Fortaleza, 60336-045, Brazil
Hospital São Lucas da PUCRS
Porto Alegre, 90610-000, Brazil
INCA - Instituto Nacional de Câncer
Rio de Janeiro, 20230-230, Brazil
NOB - Núcleo de Oncologia da Bahia
Salvador, 40170-110, Brazil
CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia - Faculdade de Medicina do ABC
Santo André, 09060-650, Brazil
Saint John Regional Hospital
Saint John, New Brunswick, E2L 4L2, Canada
Tom Baker Cancer Centre
Alberta, T2N 4N2, Canada
Stronach Regional Cancer Centre - at Southlake
Ontario, L3Y 2P9, Canada
Peking University Cancer Hospital
Beijing, 100142, China
Guangdong General Hospital
Guangzhou, 510080, China
Shanghai Cancer Hospital, Fudan University
Shanghai, 200032, China
Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha
Pessac, Gironde, 33604, France
Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie
Créteil, Val De Marne, 94010, France
Hôpital Nord - AP-HM Marseille# - Service d'Oncologie Multidisciplinaire
Bouches-du-Rhône, 13915, France
Centre Léon Bérard
Lyon, 69373, France
CHU Rennes - Hopital Pontchaillou - service de pneumologie
Rennes, 35033, France
ICO - Site René Gauducheau
Saint-Herblain, 44805, France
CHU de Toulouse - Hôpital Larrey - Service de Pneumologie et Oncologie Pneumologique
Toulouse, 31059, France
Vivantes Klinikum Am Urban - Haematologie und Onkologie
Berlin, 10967, Germany
Asklepios Fachkliniken Muenchen-Gauting - Abteilung Internistische Onkologie
Gauting, 82131, Germany
LungenClinic Grosshansdorf
Großhansdorf, 22927, Germany
Medizinische Hochschule Hannover - Pneumologie
Hanover, 30625, Germany
Universitaetsklinikum Schleswig- Holstein Campus Luebeck
Lübeck, 23538, Germany
Universitaetsklinikum Regensburg - Klinik und Poliklinik fuer Innere Medizin II
Regensburg, Germany
251 General Air Force Hospital
Athens, 11525, Greece
General Hospital of Athens of Chest Disease "SOTIRIA"
Athens, 11527, Greece
University General Hospital of Heraklion "PAGNI"
Heraklion, 71110, Greece
General Hospital Papageorgiou-2nd Department of Dermatalogy
Thessaloniki, 56429, Greece
Princess Margaret Hospital
Hong Kong, 00000, Hong Kong
The University of Hong Kong
Hong Kong, Hong Kong
The Chinese University of Hong Kong - Emergency Medicine
Shatin, 00000, Hong Kong
Azienda Ospedaliera San Giuseppe Moscati - U.O Oncologia Medica
Avellino, 83100, Italy
IRCCS Centro di Riferimento Oncologico - Oncologia Medica A
Aviano, 33081, Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Oncologia Medica
Bologna, 40138, Italy
Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico - Unità Operativa di Oncologia
Catania, 95123, Italy
Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario - Centro Oncologico
Catanzaro, 88100, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori - Medicina Oncologica I
Milan, 20133, Italy
Università degli studi della Campania Luigi Vanvitelli - Dipartimento di Oncologia
Napoli, 80131, Italy
NHO Hokkaido Cancer Center - Dept of Respiratory Medicine
Sapporo, Hokkaido, 003-0804, Japan
National Cancer Center Hospital - Dept of Respiratory Medicine
Chūōku, 104-0045, Japan
Saitama Medical University International Medical Center - Dept of Respiratory Medicine
Hidaka-shi, Japan
Saitama Cancer Center
Kitaadachigun, 362-0806, Japan
Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine
Kōtoku, 135-8550, Japan
Kurume University Hospital
Kurume-shi, 830-0011, Japan
Osaka Medical Center for Cancer and Cardiovascular Diseases
Osaka, 541-8567, Japan
Kindai University Hospital
Osakasayama-sh, 589-8511, Japan
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, 1066 CX, Netherlands
VU Medisch Centrum
Amsterdam, 1081 HV, Netherlands
Universitair Medisch Centrum Groningen (UMCG) - Parent
Groningen, 9713 GZ, Netherlands
Maastricht University Medical Center - Dept of Medical Oncology
Maastricht, 6202 AZ, Netherlands
Erasmus Medisch Centrum
Rotterdam, 3015 CE, Netherlands
St. Elisabeth Ziekenhuis - Parent
Tilburg, 5022 GC, Netherlands
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620, South Korea
Chungbuk National University Hospital
Cheongju-si, North Chungcheong, 28644, South Korea
Gachon University Gil Medical Center
Incheon, 21565, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital, Yonsei University
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Hospital del Mar - Servicio de Oncologia
Barcelona, 08003, Spain
Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica
Barcelona, 08028, Spain
Hospital Universitari Vall d'Hebron - Dept of Oncology
Barcelona, 08035, Spain
ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
L'Hospitalet de Llobregat, 08908, Spain
Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
Madrid, 28007, Spain
Hospital Universitario 12 de Octubre - Servicio de Oncologia
Madrid, 28041, Spain
Hospital Regional Universitario de Malaga
Málaga, 29010, Spain
Hospital Universitario Virgen Macarena - Servicio de Oncologia
Seville, 41009, Spain
Hospital Universitario Virgen del Rocio - Servicio de Oncologia
Seville, 41013, Spain
Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
Valencia, 46026, Spain
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
National Taiwan University Hospital
Taipei, 100, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Tri-Service General Hospital
Taipei, 11490, Taiwan
Adana Numune Training and Research Hospital - Cardiology Department
Adana, 01370, Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital - Oncology Department
Ankara, 06105, Turkey (Türkiye)
Trakya University Medical Faculty - Medical Oncology
Edirne, 22030, Turkey (Türkiye)
Kocaeli University Research and Application Hospital
Kocaeli, 41380, Turkey (Türkiye)
CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU - Ch of Oncology and MR
Dnipro, 49102, Ukraine
CI Transcarpathian Cl Onc Center Dep of Surgery#1 SHEI Ivano-Frankivsk NMU - Chair of Oncology
Ivano-Frankivsk, 76018, Ukraine
Communal Non-profit Enterprise Regional Center of Oncology - Parent
Kharkiv, 61070, Ukraine
Medical and Preventive Treatment Institution Volyn Regional Oncological Dispensary - Dept of Oncochemotherapy
Lutsk, 43018, Ukraine
CCCH City Oncological Center SHEI Uzhgorod NU - Ch of R&O of Faculty of PGE&PUT
Uzhhorod, 88000, Ukraine
Medical center "Oncolife"
Zaporizhzhia, 69059, Ukraine
Related Publications (3)
Brown T, Pilkington G, Bagust A, Boland A, Oyee J, Tudur-Smith C, Blundell M, Lai M, Martin Saborido C, Greenhalgh J, Dundar Y, Dickson R. Clinical effectiveness and cost-effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer: a systematic review and economic evaluation. Health Technol Assess. 2013 Jul;17(31):1-278. doi: 10.3310/hta17310.
PMID: 23886301RESULTCho BC, Lee JS, Wu YL, Cicin I, Dols MC, Ahn MJ, Cuppens K, Veillon R, Nadal E, Dias JM, Martin C, Reck M, Garon EB, Felip E, Paz-Ares L, Mornex F, Vokes EE, Adjei AA, Robinson C, Sato M, Vugmeyster Y, Machl A, Audhuy F, Chaudhary S, Barlesi F. Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1-High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial. J Thorac Oncol. 2023 Dec;18(12):1731-1742. doi: 10.1016/j.jtho.2023.08.018. Epub 2023 Aug 18.
PMID: 37597750RESULTMilenkovic-Grisic AM, Terranova N, Mould DR, Vugmeyster Y, Mrowiec T, Machl A, Girard P, Venkatakrishnan K, Khandelwal A. Tumor growth inhibition modeling in patients with second line biliary tract cancer and first line non-small cell lung cancer based on bintrafusp alfa trials. CPT Pharmacometrics Syst Pharmacol. 2024 Jan;13(1):143-153. doi: 10.1002/psp4.13068. Epub 2023 Dec 13.
PMID: 38087967DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Communication Center
- Organization
- Merck KGaA, Darmstadt, Germany
Study Officials
- STUDY DIRECTOR
Medical Responsible
Merck KGaA, Darmstadt, Germany
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 9, 2018
First Posted
August 15, 2018
Study Start
October 1, 2018
Primary Completion
June 7, 2021
Study Completion
June 25, 2024
Last Updated
April 8, 2025
Results First Posted
June 29, 2022
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
- Time Frame
- Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
- Access Criteria
- Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21