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)

March 21, 2025 updated by: EMD Serono Research & Development Institute, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

304

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 Locations

  • Argentina
      • Berazategui, Argentina, B1880BBF
        • Centro de Oncologia e Investigacion Buenos Aires
      • Ciudad Autonoma Buenos Aires, Argentina, C1426ANZ
        • Instituto Médico Especializado Alexander Fleming
      • Cordoba, Argentina, X5000JHQ
        • Sanatorio Allende
      • Rio Cuarto, Argentina, 5800
        • Instituto Médico Río Cuarto
      • Rosario, Argentina, S2000KZE
        • Instituto de Oncologia de Rosario
      • San Miguel de Tucuman, Argentina, 4000
        • Centro Medico San Roque S.R.L.
  • Belgium
      • Bruxelles, Belgium, 1090
        • Universitair Ziekenhuis Brussel - Geriatrie
      • Hasselt, Belgium, 3500
        • Jessa Ziekenhuis Hospital
      • Pellenberg, Belgium, 3212
        • UZ Leuven
      • Yvoir, Belgium, 5530
        • CHU Mont-Godinne
  • Brazil
      • Barretos, Brazil, 14784-400
        • Hospital de Cancer de Barretos - Fundacao Pio XII
      • Fortaleza, Brazil, 60336-045
        • Crio - Centro Regional Integrado de Oncologia
      • Porto Alegre, Brazil, 90610-000
        • Hospital São Lucas da PUCRS
      • Rio de Janeiro, Brazil, 20230-230
        • INCA - Instituto Nacional de Cancer
      • Salvador, Brazil, 40170-110
        • NOB - Nucleo de Oncologia da Bahia
      • Santo Andre, Brazil, 09060-650
        • CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia - Faculdade de Medicina do ABC
  • Canada
      • Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
      • Ontario, Canada, L3Y 2P9
        • Stronach Regional Cancer Centre - at Southlake
    • New Brunswick
      • St. John, New Brunswick, Canada, E2L 4L2
        • Saint John Regional Hospital
  • China
      • Beijing, China, 100142
        • Peking University Cancer Hospital
      • Guangzhou, China, 510080
        • Guangdong General Hospital
      • Shanghai, China, 200032
        • Shanghai Cancer Hospital, Fudan University
  • France
      • Bouches-du-Rhône, France, 13915
        • Hôpital Nord - AP-HM Marseille# - Service d'Oncologie Multidisciplinaire
      • Lyon Cedex 08, France, 69373
        • Centre Leon Berard
      • Rennes cedex 09, France, 35033
        • CHU Rennes - Hopital Pontchaillou - service de pneumologie
      • Saint Herblain, France, 44805
        • ICO - Site René Gauducheau
      • Toulouse, France, 31059
        • CHU de Toulouse - Hôpital Larrey - Service de Pneumologie et Oncologie Pneumologique
    • Gironde
      • Pessac, Gironde, France, 33604
        • Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha
    • Val De Marne
      • Creteil Cedex, Val De Marne, France, 94010
        • Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie
  • Germany
      • Berlin, Germany, 10967
        • Vivantes Klinikum Am Urban - Haematologie und Onkologie
      • Gauting, Germany, 82131
        • Asklepios Fachkliniken Muenchen-Gauting - Abteilung internistische Onkologie
      • Grosshansdorf, Germany, 22927
        • LungenClinic Grosshansdorf
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover - Pneumologie
      • Luebeck, Germany, 23538
        • Universitaetsklinikum Schleswig- Holstein Campus Luebeck
      • Regensburg, Germany
        • Universitaetsklinikum Regensburg - Klinik und Poliklinik fuer Innere Medizin II
  • Greece
      • Athens, Greece, 11525
        • 251 General Air Force Hospital
      • Athens, Greece, 11527
        • General Hospital of Athens of Chest Disease "SOTIRIA"
      • Heraklion, Greece, 71110
        • University General Hospital of Heraklion "PAGNI"
      • Thessaloniki, Greece, 56429
        • General Hospital Papageorgiou-2nd Department of Dermatalogy
  • Hong Kong
      • Hong Kong, Hong Kong
        • The University of Hong Kong
      • Hong Kong, Hong Kong, 00000
        • Princess Margaret Hospital
      • Shatin, Hong Kong, 00000
        • The Chinese University of Hong Kong - Emergency Medicine
  • Italy
      • Avellino, Italy, 83100
        • Azienda Ospedaliera San Giuseppe Moscati - U.O Oncologia Medica
      • Aviano, Italy, 33081
        • IRCCS Centro di Riferimento Oncologico - Oncologia Medica A
      • Bologna, Italy, 40138
        • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Oncologia Medica
      • Catania, Italy, 95123
        • Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico - Unità Operativa di Oncologia
      • Catanzaro, Italy, 88100
        • Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario - Centro Oncologico
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori - Medicina Oncologica I
      • Napoli, Italy, 80131
        • Università degli studi della Campania Luigi Vanvitelli - Dipartimento di Oncologia
  • Japan
      • Chuo-ku, Japan, 104-0045
        • National Cancer Center Hospital - Dept of Respiratory Medicine
      • Hidaka-shi, Japan
        • Saitama Medical University International Medical Center - Dept of Respiratory Medicine
      • Kitaadachigun, Japan, 362-0806
        • Saitama Cancer Center
      • Koto-ku, Japan, 135-8550
        • Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine
      • Kurume-shi, Japan, 830-0011
        • Kurume University Hospital
      • Osaka-shi, Japan, 541-8567
        • Osaka Medical Center for Cancer and Cardiovascular Diseases
      • Osakasayama-sh, Japan, 589-8511
        • Kindai University Hospital
    • Hokkaido
      • Sapporo-shi, Hokkaido, Japan, 003-0804
        • NHO Hokkaido Cancer Center - Dept of Respiratory Medicine
  • Korea, Republic of
      • Incheon, Korea, Republic of, 21565
        • Gachon University Gil Medical Center
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University
    • Chungcheongbuk-do
      • Cheongju-si, Chungcheongbuk-do, Korea, Republic of, 28644
        • Chungbuk National University Hospital
    • Gyeonggi-do
      • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • VU Medisch Centrum
      • Amsterdam, Netherlands, 1066 CX
        • Antoni van Leeuwenhoek Ziekenhuis
      • Groningen, Netherlands, 9713 GZ
        • Universitair Medisch Centrum Groningen (UMCG) - Parent
      • Maastricht, Netherlands, 6202 AZ
        • Maastricht University Medical Center - Dept of Medical Oncology
      • Rotterdam, Netherlands, 3015 CE
        • Erasmus Medisch Centrum
      • Tilburg, Netherlands, 5022 GC
        • St. Elisabeth Ziekenhuis - Parent
  • Spain
      • Barcelona, Spain, 08003
        • Hospital del Mar - Servicio de Oncologia
      • Barcelona, Spain, 08028
        • Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron - Dept of Oncology
      • L'Hospitalet de Llobregat, Spain, 08908
        • ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre - Servicio de Oncologia
      • Málaga, Spain, 29010
        • Hospital Regional Universitario de Malaga
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena - Servicio de Oncologia
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio - Servicio de Oncologia
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
  • Taiwan
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
      • Taipei, Taiwan, 11490
        • TRI-Service General Hospital
  • Turkey
      • Adana, Turkey, 01370
        • Adana Numune Training and Research Hospital - Cardiology Department
      • Ankara, Turkey, 06105
        • Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital - Oncology Department
      • Edirne, Turkey, 22030
        • Trakya University Medical Faculty - Medical Oncology
      • Kocaeli, Turkey, 41380
        • Kocaeli University Research and Application Hospital
  • Ukraine
      • Dnipro, Ukraine, 49102
        • CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU - Ch of Oncology and MR
      • Ivano-Frankivsk, Ukraine, 76018
        • CI Transcarpathian Cl Onc Center Dep of Surgery#1 SHEI Ivano-Frankivsk NMU - Chair of Oncology
      • Kharkiv, Ukraine, 61070
        • Communal Non-profit Enterprise Regional Center of Oncology - Parent
      • Lutsk, Ukraine, 43018
        • Medical and Preventive Treatment Institution Volyn Regional Oncological Dispensary - Dept of Oncochemotherapy
      • Uzhgorod, Ukraine, 88000
        • CCCH City Oncological Center SHEI Uzhgorod NU - Ch of R&O of Faculty of PGE&PUT
      • Zaporizhzhia, Ukraine, 69059
        • Medical center "Oncolife"
  • United States
    • Alabama
      • Huntsville, Alabama, United States, 35805
        • Oncology Specialties, PC; Clearview Cancer Institute
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center - Inflammatory Bowel Disease Center (Clinic
      • Orange, California, United States, 92868
        • UC Irvine Medical Center
      • San Diego, California, United States, 92120
        • Kaiser Permanente - Harbor City
      • Santa Barbara, California, United States, 93105
        • Sansum Clinic - Santa Barbara
    • Colorado
      • Colorado Springs, Colorado, United States, 80907
        • Rocky Mountain Cancer Centers - Colorado Springs, N. Nevada
    • Connecticut
      • Norwich, Connecticut, United States, 06360
        • Eastern Connecticut Hematology/Oncology Assoc.
    • Florida
      • Jacksonville, Florida, United States, 32256
        • Cancer Specialists, LLC - Department of Clinical Research
      • Pensacola, Florida, United States, 32503
        • Woodlands Medical Specialists
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Medical Center
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital - Clinical Research
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Baptist Health Lexington Oncology Associates
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64132
        • Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC - Menorah Medical Center - Oncology Account
    • Nebraska
      • Lincoln, Nebraska, United States, 68510
        • Southeast Nebraska Cancer Center
    • New Jersey
      • Paramus, New Jersey, United States, 07652
        • The Valley Hospital - Luckow Pavilion
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
      • Nashville, Tennessee, United States, 37203
        • SCRI - Tennessee Oncology
    • Texas
      • Bedford, Texas, United States, 76022
        • Texas Oncology - Bedford
      • Sugar Land, Texas, United States, 77479
        • Texas Oncology, P.A. - Sugarland
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC

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

No

Description

Inclusion Criteria:

  • 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
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • 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
  • Other protocol defined exclusion criteria could apply

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)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Pembrolizumab
Drug: Pembrolizumab
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.
Experimental: M7824
Drug: M7824
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
Time Frame: Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days
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)
Time Frame: Time from randomization of study drug assessed approximately up to 843 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 Frame: Time from first treatment assessed up to approximately 843 days
Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention.
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 Frame: Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days
Percentage of participants with unconfirmed best overall response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here.
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)
Time Frame: From first documented objective response to PD or death due to any cause, assessed approximately up to 746 days
DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.
From first documented objective response to PD or death due to any cause, assessed approximately up to 746 days

Collaborators and Investigators

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

Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

Investigators

  • Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

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

Helpful Links

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)

October 1, 2018

Primary Completion (Actual)

June 7, 2021

Study Completion (Actual)

June 25, 2024

Study Registration Dates

First Submitted

August 9, 2018

First Submitted That Met QC Criteria

August 13, 2018

First Posted (Actual)

August 15, 2018

Study Record Updates

Last Update Posted (Actual)

April 8, 2025

Last Update Submitted That Met QC Criteria

March 21, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MS200647_0037
  • 2018-001517-32 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

IPD Sharing 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

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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