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)
- Registration Number
- NCT03631706
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 304
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description M7824 M7824 - Pembrolizumab Pembrolizumab -
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) 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 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.
Overall Survival (OS) 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.
- Secondary Outcome Measures
Name Time Method 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 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.
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 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.
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 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.
Trial Locations
- Locations (119)
Cedars Sinai Medical Center - Inflammatory Bowel Disease Center (Clinic
🇺🇸Los Angeles, California, United States
Decatur Memorial Hospital - Clinical Research
🇺🇸Decatur, Illinois, United States
UPMC Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Kaiser Permanente - Harbor City
🇺🇸San Diego, California, United States
Oncology Specialties, PC; Clearview Cancer Institute
🇺🇸Huntsville, Alabama, United States
The Valley Hospital - Luckow Pavilion
🇺🇸Paramus, New Jersey, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
Sansum Clinic - Santa Barbara
🇺🇸Santa Barbara, California, United States
Cancer Specialists, LLC - Department of Clinical Research
🇺🇸Jacksonville, Florida, United States
Eastern Connecticut Hematology/Oncology Assoc.
🇺🇸Norwich, Connecticut, United States
Woodlands Medical Specialists
🇺🇸Pensacola, Florida, United States
Baptist Health Lexington Oncology Associates
🇺🇸Lexington, Kentucky, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
SCRI - Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Texas Oncology, P.A. - Sugarland
🇺🇸Sugar Land, Texas, United States
Texas Oncology - Bedford
🇺🇸Bedford, Texas, United States
Universitair Ziekenhuis Brussel - Geriatrie
🇧🇪Bruxelles, Belgium
Hospital de Câncer de Barretos - Fundação Pio XII
🇧🇷Barretos, Brazil
Hospital São Lucas da PUCRS
🇧🇷Porto Alegre, Brazil
CRIO - Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Brazil
INCA - Instituto Nacional de Câncer
🇧🇷Rio de Janeiro, Brazil
CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia - Faculdade de Medicina do ABC
🇧🇷Santo Andre, Brazil
Stronach Regional Cancer Centre - at Southlake
🇨🇦Ontario, Canada
NOB - Núcleo de Oncologia da Bahia
🇧🇷Salvador, Brazil
Saint John Regional Hospital
🇨🇦St. John, New Brunswick, Canada
Guangdong General Hospital
🇨🇳Guangzhou, China
Peking University Cancer Hospital
🇨🇳Beijing, China
Tom Baker Cancer Centre
🇨🇦Alberta, Canada
Shanghai Cancer Hospital, Fudan University
🇨🇳Shanghai, China
Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie
🇫🇷Creteil Cedex, Val De Marne, France
Centre Léon Bérard
🇫🇷Lyon Cedex 08, France
Hôpital Nord - AP-HM Marseille# - Service d'Oncologie Multidisciplinaire
🇫🇷Bouches-du-Rhône, France
CHU Rennes - Hopital Pontchaillou - service de pneumologie
🇫🇷Rennes cedex 09, France
ICO - Site René Gauducheau
🇫🇷Saint Herblain, France
CHU de Toulouse - Hôpital Larrey - Service de Pneumologie et Oncologie Pneumologique
🇫🇷Toulouse, France
Vivantes Klinikum Am Urban - Haematologie und Onkologie
🇩🇪Berlin, Germany
Asklepios Fachkliniken Muenchen-Gauting - Abteilung Internistische Onkologie
🇩🇪Gauting, Germany
LungenClinic Grosshansdorf
🇩🇪Grosshansdorf, Germany
Medizinische Hochschule Hannover - Pneumologie
🇩🇪Hannover, Germany
Universitaetsklinikum Schleswig- Holstein Campus Luebeck
🇩🇪Luebeck, Germany
Universitaetsklinikum Regensburg - Klinik und Poliklinik fuer Innere Medizin II
🇩🇪Regensburg, Germany
251 General Air Force Hospital
🇬🇷Athens, Greece
Azienda Ospedaliera San Giuseppe Moscati - U.O Oncologia Medica
🇮🇹Avellino, Italy
Princess Margaret Hospital
🇭🇰Hong Kong, Hong Kong
The University of Hong Kong
🇭🇰Hong Kong, Hong Kong
IRCCS Centro di Riferimento Oncologico - Oncologia Medica A
🇮🇹Aviano, Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Oncologia Medica
🇮🇹Bologna, Italy
Università degli studi della Campania Luigi Vanvitelli - Dipartimento di Oncologia
🇮🇹Napoli, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori - Medicina Oncologica I
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario - Centro Oncologico
🇮🇹Catanzaro, Italy
NHO Hokkaido Cancer Center - Dept of Respiratory Medicine
🇯🇵Sapporo-shi, Hokkaido, Japan
Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico - Unità Operativa di Oncologia
🇮🇹Catania, Italy
Osaka Medical Center for Cancer and Cardiovascular Diseases
🇯🇵Osaka-shi, Japan
Kindai University Hospital
🇯🇵Osakasayama-sh, Japan
Kurume University Hospital
🇯🇵Kurume-shi, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Hospital del Mar - Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
🇪🇸Madrid, Spain
Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica
🇪🇸Barcelona, Spain
ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital Universitari Vall d'Hebron - Dept of Oncology
🇪🇸Barcelona, Spain
Hospital Universitario Virgen del Rocio - Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Regional Universitario de Malaga
🇪🇸Málaga, Spain
Hospital Universitario Virgen Macarena - Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
🇪🇸Valencia, Spain
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Adana Numune Training and Research Hospital - Cardiology Department
🇹🇷Adana, Turkey
Kocaeli University Research and Application Hospital
🇹🇷Kocaeli, Turkey
Trakya University Medical Faculty - Medical Oncology
🇹🇷Edirne, Turkey
Communal Non-profit Enterprise Regional Center of Oncology - Parent
🇺🇦Kharkiv, Ukraine
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Henry Ford Medical Center
🇺🇸Detroit, Michigan, United States
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Rocky Mountain Cancer Centers - Colorado Springs, N. Nevada
🇺🇸Colorado Springs, Colorado, United States
Southeast Nebraska Cancer Center
🇺🇸Lincoln, Nebraska, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Instituto de Oncología de Rosario
🇦🇷Rosario, Argentina
General Hospital Papageorgiou-2nd Department of Dermatalogy
🇬🇷Thessaloniki, Greece
Chungbuk National University Hospital
🇰🇷Cheongju-si, Chungcheongbuk-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Hospital Universitario 12 de Octubre - Servicio de Oncologia
🇪🇸Madrid, Spain
Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital - Oncology Department
🇹🇷Ankara, Turkey
CI Transcarpathian Cl Onc Center Dep of Surgery#1 SHEI Ivano-Frankivsk NMU - Chair of Oncology
🇺🇦Ivano-Frankivsk, Ukraine
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Centro de Oncologia e Investigacion Buenos Aires
🇦🇷Berazategui, Argentina
Centro Medico San Roque S.R.L.
🇦🇷San Miguel de Tucuman, Argentina
The Chinese University of Hong Kong - Emergency Medicine
🇭🇰Shatin, Hong Kong
National Cancer Center Hospital - Dept of Respiratory Medicine
🇯🇵Chuo-ku, Japan
Maastricht University Medical Center - Dept of Medical Oncology
🇳🇱Maastricht, Netherlands
Medical and Preventive Treatment Institution Volyn Regional Oncological Dispensary - Dept of Oncochemotherapy
🇺🇦Lutsk, Ukraine
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Instituto Medico Rio Cuarto
🇦🇷Rio Cuarto, Argentina
Jessa Ziekenhuis Hospital
🇧🇪Hasselt, Belgium
Saitama Cancer Center
🇯🇵Kitaadachigun, Japan
CCCH City Oncological Center SHEI Uzhgorod NU - Ch of R&O of Faculty of PGE&PUT
🇺🇦Uzhgorod, Ukraine
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Instituto Medico Especializado Alexander Fleming
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
UZ Leuven
🇧🇪Pellenberg, Belgium
CHU Mont-Godinne
🇧🇪Yvoir, Belgium
University General Hospital of Heraklion "PAGNI"
🇬🇷Heraklion, Greece
Saitama Medical University International Medical Center - Dept of Respiratory Medicine
🇯🇵Hidaka-shi, Japan
Antoni van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU - Ch of Oncology and MR
🇺🇦Dnipro, Ukraine
Sanatorio Allende
🇦🇷Cordoba, Argentina
Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha
🇫🇷Pessac, Gironde, France
General Hospital of Athens of Chest Disease "SOTIRIA"
🇬🇷Athens, Greece
St. Elisabeth Ziekenhuis - Parent
🇳🇱Tilburg, Netherlands
Medical center "Oncolife"
🇺🇦Zaporizhzhia, Ukraine
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine
🇯🇵Koto-ku, Japan
Universitair Medisch Centrum Groningen (UMCG) - Parent
🇳🇱Groningen, Netherlands
Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC - Menorah Medical Center - Oncology Account
🇺🇸Kansas City, Missouri, United States