Clinical trial NCT03631706: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: M7824
Pembrolizumab
PD-L1-tumor Expression
INTR@PID Lung 037
Bintrafusp alfa
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2018-08-15
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
timeFrame: Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days
measure: Overall Survival (OS)
timeFrame: Time from randomization of study drug assessed approximately up to 843 days
Secondary outcomes:
measure: 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
timeFrame: Time from first treatment assessed up to approximately 843 days
measure: 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)
timeFrame: Time from randomization of study drug until the first documentation of PD or death, assessed approximately up to 746 days
measure: 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)
timeFrame: From first documented objective response to PD or death due to any cause, assessed approximately up to 746 days
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Oncology Specialties, PC; Clearview Cancer Institute
state: Alabama
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center - Inflammatory Bowel Disease Center (Clinic
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: San Diego
country: United States
facility: Kaiser Permanente - Harbor City
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic - Santa Barbara
state: California
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers - Colorado Springs, N. Nevada
state: Colorado
city: Norwich
country: United States
facility: Eastern Connecticut Hematology/Oncology Assoc.
state: Connecticut
city: Jacksonville
country: United States
facility: Cancer Specialists, LLC - Department of Clinical Research
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital - Clinical Research
state: Illinois
city: Lexington
country: United States
facility: Baptist Health Lexington Oncology Associates
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Kansas City
country: United States
facility: Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC - Menorah Medical Center - Oncology Account
state: Missouri
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Center
state: Nebraska
city: Paramus
country: United States
facility: The Valley Hospital - Luckow Pavilion
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Bedford
country: United States
facility: Texas Oncology - Bedford
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology, P.A. - Sugarland
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Berazategui
country: Argentina
facility: Centro de Oncologia e Investigacion Buenos Aires
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming
city: Cordoba
country: Argentina
facility: Sanatorio Allende
city: Rio Cuarto
country: Argentina
facility: Instituto Medico Rio Cuarto
city: Rosario
country: Argentina
facility: Instituto de Oncología de Rosario
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico San Roque S.R.L.
city: Bruxelles
country: Belgium
facility: Universitair Ziekenhuis Brussel - Geriatrie
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis Hospital
city: Pellenberg
country: Belgium
facility: UZ Leuven
city: Yvoir
country: Belgium
facility: CHU Mont-Godinne
city: Barretos
country: Brazil
facility: Hospital de Câncer de Barretos - Fundação Pio XII
city: Fortaleza
country: Brazil
facility: CRIO - Centro Regional Integrado de Oncologia
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS
city: Rio de Janeiro
country: Brazil
facility: INCA - Instituto Nacional de Câncer
city: Salvador
country: Brazil
facility: NOB - Núcleo de Oncologia da Bahia
city: Santo Andre
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia - Faculdade de Medicina do ABC
city: St. John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: Alberta
country: Canada
facility: Tom Baker Cancer Centre
city: Ontario
country: Canada
facility: Stronach Regional Cancer Centre - at Southlake
city: Beijing
country: China
facility: Peking University Cancer Hospital
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Shanghai
country: China
facility: Shanghai Cancer Hospital, Fudan University
city: Pessac
country: France
facility: Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha
state: Gironde
city: Creteil Cedex
country: France
facility: Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie
state: Val De Marne
city: Bouches-du-Rhône
country: France
facility: Hôpital Nord - AP-HM Marseille# - Service d'Oncologie Multidisciplinaire
city: Lyon Cedex 08
country: France
facility: Centre Léon Bérard
city: Rennes cedex 09
country: France
facility: CHU Rennes - Hopital Pontchaillou - service de pneumologie
city: Saint Herblain
country: France
facility: ICO - Site René Gauducheau
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital Larrey - Service de Pneumologie et Oncologie Pneumologique
city: Berlin
country: Germany
facility: Vivantes Klinikum Am Urban - Haematologie und Onkologie
city: Gauting
country: Germany
facility: Asklepios Fachkliniken Muenchen-Gauting - Abteilung Internistische Onkologie
city: Grosshansdorf
country: Germany
facility: LungenClinic Grosshansdorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover - Pneumologie
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig- Holstein Campus Luebeck
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg - Klinik und Poliklinik fuer Innere Medizin II
city: Athens
country: Greece
facility: 251 General Air Force Hospital
city: Athens
country: Greece
facility: General Hospital of Athens of Chest Disease "SOTIRIA"
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion "PAGNI"
city: Thessaloniki
country: Greece
facility: General Hospital Papageorgiou-2nd Department of Dermatalogy
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong - Emergency Medicine
city: Avellino
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati - U.O Oncologia Medica
city: Aviano
country: Italy
facility: IRCCS Centro di Riferimento Oncologico - Oncologia Medica A
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Oncologia Medica
city: Catania
country: Italy
facility: Azienda Ospedaliera Univ. Policlinico Gaspare Rodolico - Unità Operativa di Oncologia
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario - Centro Oncologico
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori - Medicina Oncologica I
city: Napoli
country: Italy
facility: Università degli studi della Campania Luigi Vanvitelli - Dipartimento di Oncologia
city: Sapporo-shi
country: Japan
facility: NHO Hokkaido Cancer Center - Dept of Respiratory Medicine
state: Hokkaido
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital - Dept of Respiratory Medicine
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center - Dept of Respiratory Medicine
city: Kitaadachigun
country: Japan
facility: Saitama Cancer Center
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine
city: Kurume-shi
country: Japan
facility: Kurume University Hospital
city: Osaka-shi
country: Japan
facility: Osaka Medical Center for Cancer and Cardiovascular Diseases
city: Osakasayama-sh
country: Japan
facility: Kindai University Hospital
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbuk-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen (UMCG) - Parent
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center - Dept of Medical Oncology
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Tilburg
country: Netherlands
facility: St. Elisabeth Ziekenhuis - Parent
city: Barcelona
country: Spain
facility: Hospital del Mar - Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Dept of Oncology
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre - Servicio de Oncologia
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena - Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Adana
country: Turkey
facility: Adana Numune Training and Research Hospital - Cardiology Department
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital - Oncology Department
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty - Medical Oncology
city: Kocaeli
country: Turkey
facility: Kocaeli University Research and Application Hospital
city: Dnipro
country: Ukraine
facility: CI Dnipropetrovsk CMCH #4 of Dnipropetrovsk RC Dept of Chemotherapy SI Dnipropetrovsk MA of MOHU - Ch of Oncology and MR
city: Ivano-Frankivsk
country: Ukraine
facility: CI Transcarpathian Cl Onc Center Dep of Surgery#1 SHEI Ivano-Frankivsk NMU - Chair of Oncology
city: Kharkiv
country: Ukraine
facility: Communal Non-profit Enterprise Regional Center of Oncology - Parent
city: Lutsk
country: Ukraine
facility: Medical and Preventive Treatment Institution Volyn Regional Oncological Dispensary - Dept of Oncochemotherapy
city: Uzhgorod
country: Ukraine
facility: CCCH City Oncological Center SHEI Uzhgorod NU - Ch of R&O of Faculty of PGE&PUT
city: Zaporizhzhia
country: Ukraine
facility: Medical center "Oncolife"
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Cho 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.