M7824 With cCRT in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC)

A Multicenter, Double Blind, Randomized, Controlled Study of M7824 With Concurrent Chemoradiation Followed by M7824 Versus Concurrent Chemoradiation Plus Placebo Followed by Durvalumab in Participants With Unresectable Stage III Non-small Cell Lung Cancer

The main purpose of this study was to evaluate safety and efficacy in participants treated with concomitant chemoradiation therapy (cCRT) plus M7824 followed by M7824 compared to cCRT plus placebo followed by durvalumab.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: M7824; Drug: Etoposide; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel; Drug: Cisplatin; Radiation: Intensity Modulated Radiation Therapy (IMRT); Drug: Placebo; Drug: Durvalumab

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina
    • Sanatorio Allende
  • San Juan, Argentina
    • Centro Polivalente de Asistencia e Inv. Clinica CER
• Australia
  • Bendigo, Australia
    • Bendigo Hospital
  • Douglas, Australia
    • The Townsville Hospital
  • Elizabeth Vale, Australia
    • Calvary Central Districts Hospital
  • Fitzroy, Australia
    • St Vincent's Hospital Melbourne - PARENT
  • Geelong, Australia
    • University Hospital Geelong - PARENT
  • Heidelberg Heights, Australia
    • Austin Health
  • Pergamino, Australia
    • Centro de Investigacion Pergamino SA
  • Randwick, Australia
    • Prince of Wales Hospital
  • St Albans, Australia
    • Sunshine Hospital
  • St Leonards, Australia
    • Royal North Shore Hospital
  • Warrnambool, Australia
    • South West Healthcare - South West Oncology
• Belgium
  • Leuven, Belgium
    • UZ Leuven
  • Namur, Belgium
    • Clinique et Maternite St Elisabeth Namur
  • Roeselare, Belgium
    • AZ Delta
  • Yvoir, Belgium
    • CHU Mont-Godinne
• Brazil
  • Barretos, Brazil
    • Hospital de Cancer de Barretos - Fundacao Pio XII
  • Itajaí, Brazil
    • Clínica de Neoplasias Litoral Ltda.
  • Porto Alegre, Brazil
    • Hospital Sao Lucas da PUCRS
  • Porto Alegre, Brazil
    • HGB - Hospital Giovanni Battista - Mãe de Deus Center - Centro de Pesquisa Clínica - Instituto do Câncer
  • Rio de Janeiro, Brazil
    • COI - Clínicas Oncológicas Integradas
  • São Paulo, Brazil
    • ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira
  • São Paulo, Brazil
    • A. C. Camargo Cancer Center - Fundação Antônio Prudente
• Canada
  • Kelowna, Canada
    • BC Cancer Agency Center for the Southern Interior
• China
  • Beijing, China
    • Peking University Cancer Hospital
  • Changchun, China
    • Jilin Cancer Hospital - Oncology
  • Hangzhou, China
    • Hangzhou First People's Hospital
• Czechia
  • Olomouc, Czechia
    • Fakultni nemocnice Olomouc - Dept of Onkologicka klinika
• France
  • Bayonne, France
    • Centre Hospitalier de la Côte Basque - Service de Pneumologie
  • Marseille cedex 20, France
    • Hôpital Nord - AP-HM Marseille# - Service d'Oncologie Multidisciplinaire
  • Paris Cedex 05, France
    • Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris - Service d'Oncologie Médicale
  • Saint Herblain, France
    • CHU Nantes - Hôpital Guillaume et René Laënnec - Service de Pneumologie
• Germany
  • Hamburg, Germany
    • Asklepios Klinik Harburg - Medizinische Abteilung I
  • Oldenburg, Germany
    • Pius-Hospital Oldenburg - Klinik f. Haematologie und Onkologie
• Japan
  • Bunkyo-ku, Japan
    • Nippon Medical School Hospital - Dept of Respiratory Medicine
  • Bunkyo-ku, Japan
    • Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital - Dept of Respiratory Medicine
  • Hidaka-shi, Japan
    • Saitama Medical University International Medical Center - Dept of Respiratory Medicine
  • Kashiwa-shi, Japan
    • National Cancer Center Hospital East - Dept of Respiratory Medicine
  • Kobe-shi, Japan
    • Kobe City Hospital Organization Kobe City Medical Center General Hospital - Dept of Respiratory Medicine
  • Koto-ku, Japan
    • Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine
  • Kurume-shi, Japan
    • Kurume University Hospital - Dept of Lung Cancer Center
  • Nagoya-shi, Japan
    • Aichi Cancer Center Hospital - Dept of Respiratory Medicine
  • Osaka-shi, Japan
    • Osaka Medical Center for Cancer and Cardiovascular Diseases
  • Osakasayama-shi, Japan
    • Kindai University Hospital (13859)
  • Sunto-gun, Japan
    • Shizuoka Cancer Center
  • Yokohama-shi, Japan
    • Kanagawa Cancer Center - Dept of Respiratory Medicine
• Korea, Republic of
  • Daegu, Korea, Republic of
    • Keimyung University Dongsan Hospital
  • Seongnam, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University
• Netherlands
  • 's Hertogenbosch, Netherlands
    • Jeroen Bosch Ziekenhuis
  • Amersfoort, Netherlands
    • Meander Medisch Centrum - Dep of Pulmonology
  • Breda, Netherlands
    • Amphia Ziekenhuis - PARENT - Parent
  • Groningen, Netherlands
    • Martini Ziekenhuis
  • Harderwijk, Netherlands
    • Ziekenhuis St. Jansdal
  • Nieuwegein, Netherlands
    • St. Antonius Ziekenhuis - Dept Pulmonology - Nieuwegein
  • Tilburg, Netherlands
    • St. Elisabeth Ziekenhuis - Parent
  • Zwolle, Netherlands
    • ISALA Klinieken Locatie Sophia
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron - Dept of Oncology
  • Barcelona, Spain
    • Hospital del Mar - Servicio de Oncologia
  • Barcelona, Spain
    • Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica
  • L'Hospitalet de Llobregat, Spain
    • ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
  • Madrid, Spain
    • Hospital Universitario Clinico San Carlos - Servicio de Oncologia
  • Madrid, Spain
    • Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre - Servicio de Oncologia
  • Madrid, Spain
    • Clinica Universidad de Navarra (MAD) - Oncology Service
  • Majadahonda, Spain
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Málaga, Spain
    • Hospital Regional Universitario de Malaga
  • Pamplona, Spain
    • Clinica Universidad de Navarra
  • Santiago de Compostela, Spain
    • Complejo Hospitalario Universitario de Santiago - Servicio de Oncologia Medica
  • Sevilla, Spain
    • Hospital Universitario Virgen Macarena - Servicio de Oncologia
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocio - Servicio de Oncologia
  • Sevilla, Spain
    • Hospital Universitario Nuestra Señora de Valme - Servicio de Oncologia
  • Valencia, Spain
    • Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
  • Vigo, Spain
    • Hospital Alvaro Cunqueiro - Servicio de Oncologia
• Taiwan
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Tainan, Taiwan
    • Chi Mei Medical Center, Liou Ying
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • Santa Monica, California, United States, 90404
      • UCLA Hematology Oncology - Main Site - 2020 Santa Monica
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • University of Colorado Health - Memorial Hospital - Memorial Hospital
    • Fort Collins, Colorado, United States, 80528
      • Hematology Oncology Associates
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute Center
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital - Michael and Dianne Bienes CCC
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center - University of Miami Health System
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan St. Francis Health Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • American Health Network of Indiana, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington Oncology Associates
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland - DUPLICATE/Pediatric Surgery
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Nyack, New York, United States, 10960
      • Hematology Oncology Center of Nyack Hospital
  • North Carolina
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas, Inc.
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The James Cancer Hospital and Solove Research Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center - Unit 432 Thoracic Head and Neck Medical Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have histologically documented NSCLC who present with Stage III locally advanced, unresectable disease (International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology
• Participants with tumor harboring an Epidermal growth factor receptor (EGFR) sensitizing (activating) mutation, Anaplastic lymphoma kinase (ALK) translocation, ROS-1 rearrangement are eligible.
• Participants must have adequate pulmonary function defined as a forced expiratory volume in 1 second (FEV1) greater than equals to (>=) 1.2 liters or >= 50% of predicted normal volume measured within 3 weeks prior to randomization.
• Adequate hematological, hepatic and renal function as defined in the protocol
• Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies

Exclusion Criteria:

• Participants with Mixed small cell with non-small cell lung cancer histology
• Recent major surgery within 4 weeks prior to entry into the study
• Significant acute or chronic infections including human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome, Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and active tuberculosis
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization
• Active autoimmune disease that has required systemic treatment in past 1 year (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
• Any prior systemic cytotoxic chemotherapy for their NSCLC or any antibody or drug targeting T-cell coregulatory proteins

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cCRT plus M7824 followed by M7824; Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824.	Drug: M7824; Participants received intravenous infusion of 1200 milligram (mg) M7824 over 1 hour every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.; Drug: Etoposide; Participants received etoposide 50 mg/m^2 intravenously over a minimum of 30 minutes up to 60 minutes daily on Day 1 to 5 and Day 29 to 33 during cCRT.; Drug: Pemetrexed; Participants received pemetrexed at a dose of 500 mg/m^2 intravenously over 10 minutes or according to local standards on Days 1, 22, and 43 during cCRT.; Drug: Carboplatin; Participants received carboplatin intravenously based on area under curve (AUC) 2 over 30 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.; Drug: Paclitaxel; Participants received paclitaxel intravenously at a dose of 45 mg/m^2 over 60 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.; Drug: Cisplatin; In combination with etoposide, participants received cisplatin 50 mg/m^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants received cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT.; Radiation: Intensity Modulated Radiation Therapy (IMRT); Participants received IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).
Active Comparator: cCRT plus placebo followed by durvalumab; Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with placebo matched to M7824 followed by durvalumab.	Drug: Etoposide; Participants received etoposide 50 mg/m^2 intravenously over a minimum of 30 minutes up to 60 minutes daily on Day 1 to 5 and Day 29 to 33 during cCRT.; Drug: Pemetrexed; Participants received pemetrexed at a dose of 500 mg/m^2 intravenously over 10 minutes or according to local standards on Days 1, 22, and 43 during cCRT.; Drug: Carboplatin; Participants received carboplatin intravenously based on area under curve (AUC) 2 over 30 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.; Drug: Paclitaxel; Participants received paclitaxel intravenously at a dose of 45 mg/m^2 over 60 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.; Drug: Cisplatin; In combination with etoposide, participants received cisplatin 50 mg/m^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants received cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT.; Radiation: Intensity Modulated Radiation Therapy (IMRT); Participants received IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).; Drug: Placebo; Participants received intravenous infusion of placebo matched to M7824 over 1 hour q2w during cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.; Drug: Durvalumab; Participants received intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) over 1 hour q2w up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

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 Investigator	PFS was defined as the time from randomization to the date of 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. PFS was analyzed by using the Kaplan-Meier method.	Time from randomization to the date of first documentation of PD or death, assessed approximately up to 27 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events	Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily have 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 randomization up to data cut off (assessed up to 27 months)
Overall Survival (OS)	Overall Survival was defined as the time from randomization to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method.	Time from randomization to the date of death due to any cause, assessed up to 27 months
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator	ORR was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to RECIST v1.1as adjudicated by the Investigator. CR: Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions.	Time from randomization up to data cut off (assessed up to 27 months)
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator	DOR was defined 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.	Time from first documentation of objective response to the date of first documentation of PD or death due to any cause, assessed approximately up to 27 months
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of M7824	Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed M7824 concentration-time data.	Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343
Serum Concentration Immediately Before Next Dosing (Ctrough) of M7824	Ctrough was the serum concentration observed immediately before next dosing.	Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343
Number of Participants With Positive Antidrug Antibodies (ADA)	Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.	Time from randomization up to data cut off (assessed up to 27 months)

Collaborators and Investigators

• 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

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2019
• Primary Completion (Actual): February 17, 2023
• Study Completion (Actual): February 17, 2023

Study Registration Dates

• First Submitted: February 12, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: M7824; Non-small Cell Lung Cancer; Durvalumab; Stage III; Bintrafusp alfa (proposed INN); INTR@PID LUNG 005
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Etoposide; Paclitaxel; Durvalumab; Pemetrexed
• Other Study ID Numbers: MS200647_0005; 2018-003265-34 (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; 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