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)

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03631706
• Other study ID #: MS200647_0037
• Secondary ID: 2018-001517-32
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 1, 2018
• Est. completion date: June 30, 2024

Study information

• Verified date: February 2024
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 304
• Est. completion date: June 30, 2024
• Est. primary completion date: June 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.
• 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.

Locations

Country	Name	City	State
Argentina	Centro de Oncologia e Investigacion Buenos Aires	Berazategui
Argentina	Instituto Medico Especializado Alexander Fleming	Ciudad Autonoma Buenos Aires
Argentina	Sanatorio Allende	Cordoba
Argentina	Instituto Medico Rio Cuarto	Rio Cuarto
Argentina	Instituto de Oncología de Rosario	Rosario
Argentina	Centro Medico San Roque S.R.L.	San Miguel de Tucuman
Belgium	Universitair Ziekenhuis Brussel - Geriatrie	Bruxelles
Belgium	Jessa Ziekenhuis Hospital	Hasselt
Belgium	UZ Leuven	Pellenberg
Belgium	CHU Mont-Godinne	Yvoir
Brazil	Hospital de Câncer de Barretos - Fundação Pio XII	Barretos
Brazil	CRIO - Centro Regional Integrado de Oncologia	Fortaleza
Brazil	Hospital São Lucas da PUCRS	Porto Alegre
Brazil	INCA - Instituto Nacional de Câncer	Rio de Janeiro
Brazil	NOB - Núcleo de Oncologia da Bahia	Salvador
Brazil	CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia - Faculdade de Medicina do ABC	Santo Andre
Canada	Tom Baker Cancer Centre	Alberta
Canada	Stronach Regional Cancer Centre - at Southlake	Ontario
Canada	Saint John Regional Hospital	St. John	New Brunswick
China	Peking University Cancer Hospital	Beijing
China	Guangdong General Hospital	Guangzhou
China	Shanghai Cancer Hospital, Fudan University	Shanghai
France	Hôpital Nord - AP-HM Marseille# - Service d'Oncologie Multidisciplinaire	Bouches-du-Rhône
France	Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie	Creteil Cedex	Val De Marne
France	Centre Léon Bérard	Lyon Cedex 08
France	Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha	Pessac	Gironde
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
Germany	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
Greece	251 General Air Force Hospital	Athens
Greece	General Hospital of Athens of Chest Disease "SOTIRIA"	Athens
Greece	University General Hospital of Heraklion "PAGNI"	Heraklion
Greece	General Hospital Papageorgiou-2nd Department of Dermatalogy	Thessaloniki
Hong Kong	Princess Margaret Hospital	Hong Kong
Hong Kong	The University of Hong Kong	Hong Kong
Hong Kong	The Chinese University of Hong Kong - Emergency Medicine	Shatin
Italy	Azienda Ospedaliera San Giuseppe Moscati - U.O Oncologia Medica	Avellino
Italy	IRCCS Centro di Riferimento Oncologico - Oncologia Medica A	Aviano
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Oncologia Medica	Bologna
Italy	Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico - Unità Operativa di Oncologia	Catania
Italy	Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario - Centro Oncologico	Catanzaro
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori - Medicina Oncologica I	Milano
Italy	Università degli studi della Campania Luigi Vanvitelli - Dipartimento di Oncologia	Napoli
Japan	National Cancer Center Hospital - Dept of Respiratory Medicine	Chuo-ku
Japan	Saitama Medical University International Medical Center - Dept of Respiratory Medicine	Hidaka-shi
Japan	Saitama Cancer Center	Kitaadachigun
Japan	Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine	Koto-ku
Japan	Kurume University Hospital	Kurume-shi
Japan	Osaka Medical Center for Cancer and Cardiovascular Diseases	Osaka-shi
Japan	Kindai University Hospital	Osakasayama-sh
Japan	NHO Hokkaido Cancer Center - Dept of Respiratory Medicine	Sapporo-shi	Hokkaido
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Netherlands	Antoni van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	VU Medisch Centrum	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen (UMCG) - Parent	Groningen
Netherlands	Maastricht University Medical Center - Dept of Medical Oncology	Maastricht
Netherlands	Erasmus Medisch Centrum	Rotterdam
Netherlands	St. Elisabeth Ziekenhuis - Parent	Tilburg
Spain	Hospital del Mar - Servicio de Oncologia	Barcelona
Spain	Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica	Barcelona
Spain	Hospital Universitari Vall d'Hebron - Dept of Oncology	Barcelona
Spain	ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia	L'Hospitalet de Llobregat
Spain	Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica	Madrid
Spain	Hospital Universitario 12 de Octubre - Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario de Malaga	Málaga
Spain	Hospital Universitario Virgen del Rocio - Servicio de Oncologia	Sevilla
Spain	Hospital Universitario Virgen Macarena - Servicio de Oncologia	Sevilla
Spain	Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica	Valencia
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Turkey	Adana Numune Training and Research Hospital - Cardiology Department	Adana
Turkey	Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital - Oncology Department	Ankara
Turkey	Trakya University Medical Faculty - Medical Oncology	Edirne
Turkey	Kocaeli University Research and Application Hospital	Kocaeli
Ukraine	CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU - Ch of Oncology and MR	Dnipro
Ukraine	CI Transcarpathian Cl Onc Center Dep of Surgery#1 SHEI Ivano-Frankivsk NMU - Chair of Oncology	Ivano-Frankivsk
Ukraine	Communal Non-profit Enterprise Regional Center of Oncology - Parent	Kharkiv
Ukraine	Medical and Preventive Treatment Institution Volyn Regional Oncological Dispensary - Dept of Oncochemotherapy	Lutsk
Ukraine	CCCH City Oncological Center SHEI Uzhgorod NU - Ch of R&O of Faculty of PGE&PUT	Uzhgorod
Ukraine	Medical center "Oncolife"	Zaporizhzhia
United States	Texas Oncology - Bedford	Bedford	Texas
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Rocky Mountain Cancer Centers - Colorado Springs, N. Nevada	Colorado Springs	Colorado
United States	Decatur Memorial Hospital - Clinical Research	Decatur	Illinois
United States	Henry Ford Medical Center	Detroit	Michigan
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Oncology Specialties, PC; Clearview Cancer Institute	Huntsville	Alabama
United States	Cancer Specialists, LLC - Department of Clinical Research	Jacksonville	Florida
United States	Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC - Menorah Medical Center - Oncology Account	Kansas City	Missouri
United States	Baptist Health Lexington Oncology Associates	Lexington	Kentucky
United States	Southeast Nebraska Cancer Center	Lincoln	Nebraska
United States	Cedars Sinai Medical Center - Inflammatory Bowel Disease Center (Clinic	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	SCRI - Tennessee Oncology	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Eastern Connecticut Hematology/Oncology Assoc.	Norwich	Connecticut
United States	UC Irvine Medical Center	Orange	California
United States	The Valley Hospital - Luckow Pavilion	Paramus	New Jersey
United States	Woodlands Medical Specialists	Pensacola	Florida
United States	UPMC Cancer Center	Pittsburgh	Pennsylvania
United States	University of Rochester Medical Center	Rochester	New York
United States	Kaiser Permanente - Harbor City	San Diego	California
United States	Sansum Clinic - Santa Barbara	Santa Barbara	California
United States	Texas Oncology, P.A. - Sugarland	Sugar Land	Texas

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  China,  France,  Germany,  Greece,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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	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
Secondary	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)	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
Secondary	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)	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

External Links

•   Trial Awareness and Transparency website