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

NCT ID: NCT03840902

Last Updated: 2024-01-16

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

153 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-16

Study Completion Date

2023-02-17

Brief Summary

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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.

Detailed Description

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Conditions

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Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

M7824

Intervention Type DRUG

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.

Etoposide

Intervention Type DRUG

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.

Pemetrexed

Intervention Type DRUG

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.

Carboplatin

Intervention Type DRUG

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.

Paclitaxel

Intervention Type DRUG

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.

Cisplatin

Intervention Type DRUG

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.

Intensity Modulated Radiation Therapy (IMRT)

Intervention Type RADIATION

Participants received IMRT 5 fractions per week for about 6 weeks (Total 60 gray \[Gy\]).

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.

Group Type ACTIVE_COMPARATOR

Placebo

Intervention Type DRUG

Participants received intravenous infusion of placebo matched to M7824 over 1 hour q2w during cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.

Durvalumab

Intervention Type DRUG

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.

Etoposide

Intervention Type DRUG

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.

Pemetrexed

Intervention Type DRUG

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.

Carboplatin

Intervention Type DRUG

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.

Paclitaxel

Intervention Type DRUG

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.

Cisplatin

Intervention Type DRUG

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.

Intensity Modulated Radiation Therapy (IMRT)

Intervention Type RADIATION

Participants received IMRT 5 fractions per week for about 6 weeks (Total 60 gray \[Gy\]).

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Intensity Modulated Radiation Therapy (IMRT)

Participants received IMRT 5 fractions per week for about 6 weeks (Total 60 gray \[Gy\]).

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

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University of California Irvine Medical Center

Orange, California, United States

Site Status

UCLA Hematology Oncology - Main Site - 2020 Santa Monica

Santa Monica, California, United States

Site Status

University of Colorado Health - Memorial Hospital - Memorial Hospital

Colorado Springs, Colorado, United States

Site Status

Hematology Oncology Associates

Fort Collins, Colorado, United States

Site Status

Lynn Cancer Institute Center

Boca Raton, Florida, United States

Site Status

Holy Cross Hospital - Michael and Dianne Bienes CCC

Fort Lauderdale, Florida, United States

Site Status

Sylvester Comprehensive Cancer Center - University of Miami Health System

Miami, Florida, United States

Site Status

The University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

American Health Network of Indiana, LLC

Indianapolis, Indiana, United States

Site Status

Franciscan St. Francis Health Cancer Center

Indianapolis, Indiana, United States

Site Status

Baptist Health Lexington Oncology Associates

Lexington, Kentucky, United States

Site Status

University of Maryland - DUPLICATE/Pediatric Surgery

Baltimore, Maryland, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Hematology Oncology Center of Nyack Hospital

Nyack, New York, United States

Site Status

FirstHealth of the Carolinas, Inc.

Pinehurst, North Carolina, United States

Site Status

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Site Status

UPMC Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Texas MD Anderson Cancer Center - Unit 432 Thoracic Head and Neck Medical Oncology

Houston, Texas, United States

Site Status

Sanatorio Allende

Córdoba, , Argentina

Site Status

Centro Polivalente de Asistencia e Inv. Clinica CER

San Juan, , Argentina

Site Status

Bendigo Hospital

Bendigo, , Australia

Site Status

The Townsville Hospital

Douglas, , Australia

Site Status

Calvary Central Districts Hospital

Elizabeth Vale, , Australia

Site Status

St Vincent's Hospital Melbourne - PARENT

Fitzroy, , Australia

Site Status

University Hospital Geelong - PARENT

Geelong, , Australia

Site Status

Austin Health

Heidelberg Heights, , Australia

Site Status

Centro de Investigacion Pergamino SA

Pergamino, , Australia

Site Status

Prince of Wales Hospital

Randwick, , Australia

Site Status

Sunshine Hospital

St Albans, , Australia

Site Status

Royal North Shore Hospital

St Leonards, , Australia

Site Status

South West Healthcare - South West Oncology

Warrnambool, , Australia

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Clinique et Maternite St Elisabeth Namur

Namur, , Belgium

Site Status

AZ Delta

Roeselare, , Belgium

Site Status

CHU Mont-Godinne

Yvoir, , Belgium

Site Status

Hospital de Câncer de Barretos - Fundação Pio XII

Barretos, , Brazil

Site Status

Clínica de Neoplasias Litoral Ltda.

Itajaí, , Brazil

Site Status

HGB - Hospital Giovanni Battista - Mãe de Deus Center - Centro de Pesquisa Clínica - Instituto do Câncer

Porto Alegre, , Brazil

Site Status

Hospital São Lucas da PUCRS

Porto Alegre, , Brazil

Site Status

COI - Clínicas Oncológicas Integradas

Rio de Janeiro, , Brazil

Site Status

A. C. Camargo Cancer Center - Fundação Antônio Prudente

São Paulo, , Brazil

Site Status

ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira

São Paulo, , Brazil

Site Status

BC Cancer Agency Center for the Southern Interior

Kelowna, , Canada

Site Status

Peking University Cancer Hospital

Beijing, , China

Site Status

Jilin Cancer Hospital - Oncology

Changchun, , China

Site Status

Hangzhou First People's Hospital

Hangzhou, , China

Site Status

Fakultni nemocnice Olomouc - Dept of Onkologicka klinika

Olomouc, , Czechia

Site Status

Centre Hospitalier de la Côte Basque - Service de Pneumologie

Bayonne, , France

Site Status

Hôpital Nord - AP-HM Marseille# - Service d'Oncologie Multidisciplinaire

Marseille, , France

Site Status

Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris - Service d'Oncologie Médicale

Paris, , France

Site Status

CHU Nantes - Hôpital Guillaume et René Laënnec - Service de Pneumologie

Saint-Herblain, , France

Site Status

Asklepios Klinik Harburg - Medizinische Abteilung I

Hamburg, , Germany

Site Status

Pius-Hospital Oldenburg - Klinik f. Haematologie und Onkologie

Oldenburg, , Germany

Site Status

Nippon Medical School Hospital - Dept of Respiratory Medicine

Bunkyō City, , Japan

Site Status

Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital - Dept of Respiratory Medicine

Bunkyō City, , Japan

Site Status

Saitama Medical University International Medical Center - Dept of Respiratory Medicine

Hidaka-shi, , Japan

Site Status

National Cancer Center Hospital East - Dept of Respiratory Medicine

Kashiwa-shi, , Japan

Site Status

Kobe City Hospital Organization Kobe City Medical Center General Hospital - Dept of Respiratory Medicine

Kobe, , Japan

Site Status

Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine

Kōtoku, , Japan

Site Status

Kurume University Hospital - Dept of Lung Cancer Center

Kurume-shi, , Japan

Site Status

Aichi Cancer Center Hospital - Dept of Respiratory Medicine

Nagoya, , Japan

Site Status

Osaka Medical Center for Cancer and Cardiovascular Diseases

Osaka, , Japan

Site Status

Kindai University Hospital (13859)

Osakasayama-shi, , Japan

Site Status

Shizuoka Cancer Center

Sunto-gun, , Japan

Site Status

Kanagawa Cancer Center - Dept of Respiratory Medicine

Yokohama, , Japan

Site Status

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Site Status

Meander Medisch Centrum - Dep of Pulmonology

Amersfoort, , Netherlands

Site Status

Amphia Ziekenhuis - PARENT - Parent

Breda, , Netherlands

Site Status

Martini ziekenhuis

Groningen, , Netherlands

Site Status

Ziekenhuis St. Jansdal

Harderwijk, , Netherlands

Site Status

St. Antonius Ziekenhuis - Dept Pulmonology - Nieuwegein

Nieuwegein, , Netherlands

Site Status

St. Elisabeth Ziekenhuis - Parent

Tilburg, , Netherlands

Site Status

ISALA Klinieken Locatie Sophia

Zwolle, , Netherlands

Site Status

Keimyung University Dongsan Hospital

Daegu, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University

Seoul, , South Korea

Site Status

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

Hospital del Mar - Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron - Dept of Oncology

Barcelona, , Spain

Site Status

ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia

L'Hospitalet de Llobregat, , Spain

Site Status

Clinica Universidad de Navarra (MAD) - Oncology Service

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario Clinico San Carlos - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, , Spain

Site Status

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status

Complejo Hospitalario Universitario de Santiago - Servicio de Oncologia Medica

Santiago de Compostela, , Spain

Site Status

Hospital Universitario Nuestra Señora de Valme - Servicio de Oncologia

Seville, , Spain

Site Status

Hospital Universitario Virgen del Rocio - Servicio de Oncologia

Seville, , Spain

Site Status

Hospital Universitario Virgen Macarena - Servicio de Oncologia

Seville, , Spain

Site Status

Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica

Valencia, , Spain

Site Status

Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica

Valencia, , Spain

Site Status

Hospital Alvaro Cunqueiro - Servicio de Oncologia

Vigo, , Spain

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

Chi Mei Medical Center, Liou Ying

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Tri-Service General Hospital

Taipei, , Taiwan

Site Status

Countries

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United States Argentina Australia Belgium Brazil Canada China Czechia France Germany Japan Netherlands South Korea Spain Taiwan

References

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Huang Y, Zhao JJ, Soon YY, Wong A, Aminkeng F, Ang Y, Asokumaran Y, Low JL, Lee M, Choo JRE, Chan G, Kee A, Tay SH, Goh BC, Soo RA. Real-world experience of consolidation durvalumab after concurrent chemoradiotherapy in stage III non-small cell lung cancer. Thorac Cancer. 2022 Nov;13(22):3152-3161. doi: 10.1111/1759-7714.14667. Epub 2022 Sep 30.

Reference Type DERIVED
PMID: 36177913 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2018-003265-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200647_0005

Identifier Type: -

Identifier Source: org_study_id

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