M7824 With cCRT in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC)
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Drug: PlaceboRadiation: Intensity Modulated Radiation Therapy (IMRT)
- Registration Number
- NCT03840902
- Brief Summary
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
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 153
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description cCRT plus placebo followed by durvalumab Intensity Modulated Radiation Therapy (IMRT) 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. cCRT plus M7824 followed by M7824 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. cCRT plus M7824 followed by M7824 Intensity Modulated Radiation Therapy (IMRT) Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824. cCRT plus placebo followed by durvalumab Placebo 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. cCRT plus placebo followed by durvalumab Etoposide 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. cCRT plus M7824 followed by M7824 Etoposide Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824. cCRT plus M7824 followed by M7824 Pemetrexed Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824. cCRT plus M7824 followed by M7824 Carboplatin Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824. cCRT plus M7824 followed by M7824 Paclitaxel Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824. cCRT plus M7824 followed by M7824 Cisplatin Participants received cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824. cCRT plus placebo followed by durvalumab Pemetrexed 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. cCRT plus placebo followed by durvalumab 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. cCRT plus placebo followed by durvalumab Carboplatin 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. cCRT plus placebo followed by durvalumab Paclitaxel 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. cCRT plus placebo followed by durvalumab Cisplatin 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.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator Time from randomization to the date of first documentation of PD or death, assessed approximately up to 27 months 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.
- Secondary Outcome Measures
Name Time Method Serum Concentration Immediately Before Next Dosing (Ctrough) of M7824 Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343 Ctrough was the serum concentration observed immediately before next dosing.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events Time from randomization up to data cut off (assessed up to 27 months) 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.
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of M7824 Pre-dose, 30 minutes after end of infusion on Day 1, 15, 29, 57, 85, 127, 157, 343 Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed M7824 concentration-time data.
Number of Participants With Positive Antidrug Antibodies (ADA) Time from randomization up to data cut off (assessed up to 27 months) 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.
Overall Survival (OS) Time from randomization to the date of death due to any cause, assessed up to 27 months 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.
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator Time from randomization up to data cut off (assessed up to 27 months) 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.
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator 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 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.
Trial Locations
- Locations (104)
University of Texas MD Anderson Cancer Center - Unit 432 Thoracic Head and Neck Medical Oncology
🇺🇸Houston, Texas, United States
Lynn Cancer Institute Center
🇺🇸Boca Raton, Florida, United States
American Health Network of Indiana, LLC
🇺🇸Indianapolis, Indiana, United States
Franciscan St. Francis Health Cancer Center
🇺🇸Indianapolis, Indiana, United States
Baptist Health Lexington Oncology Associates
🇺🇸Lexington, Kentucky, United States
Hospital del Mar - Servicio de Oncologia
🇪🇸Barcelona, Spain
COI - Clínicas Oncológicas Integradas
🇧🇷Rio de Janeiro, Brazil
University of Maryland - DUPLICATE/Pediatric Surgery
🇺🇸Baltimore, Maryland, United States
The James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Hospital de Câncer de Barretos - Fundação Pio XII
🇧🇷Barretos, Brazil
Hematology Oncology Center of Nyack Hospital
🇺🇸Nyack, New York, United States
University Hospital Geelong - PARENT
🇦🇺Geelong, Australia
Royal North Shore Hospital
🇦🇺St Leonards, Australia
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Centro de Investigacion Pergamino SA
🇦🇺Pergamino, Australia
Calvary Central Districts Hospital
🇦🇺Elizabeth Vale, Australia
BC Cancer Agency Center for the Southern Interior
🇨🇦Kelowna, Canada
Clinique et Maternite St Elisabeth Namur
🇧🇪Namur, Belgium
HGB - Hospital Giovanni Battista - Mãe de Deus Center - Centro de Pesquisa Clínica - Instituto do Câncer
🇧🇷Porto Alegre, Brazil
Peking University Cancer Hospital
🇨🇳Beijing, China
Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris - Service d'Oncologie Médicale
🇫🇷Paris Cedex 05, France
The Townsville Hospital
🇦🇺Douglas, Australia
Austin Health
🇦🇺Heidelberg Heights, Australia
FirstHealth of the Carolinas, Inc.
🇺🇸Pinehurst, North Carolina, United States
Asklepios Klinik Harburg - Medizinische Abteilung I
🇩🇪Hamburg, Germany
Prince of Wales Hospital
🇦🇺Randwick, Australia
Hôpital Nord - AP-HM Marseille# - Service d'Oncologie Multidisciplinaire
🇫🇷Marseille cedex 20, France
Pius-Hospital Oldenburg - Klinik f. Haematologie und Onkologie
🇩🇪Oldenburg, Germany
ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira
🇧🇷São Paulo, Brazil
Fakultni nemocnice Olomouc - Dept of Onkologicka klinika
🇨🇿Olomouc, Czechia
CHU Nantes - Hôpital Guillaume et René Laënnec - Service de Pneumologie
🇫🇷Saint Herblain, France
A. C. Camargo Cancer Center - Fundação Antônio Prudente
🇧🇷São Paulo, Brazil
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
ISALA Klinieken Locatie Sophia
🇳🇱Zwolle, Netherlands
Complejo Hospitalario Universitario de Santiago - Servicio de Oncologia Medica
🇪🇸Santiago de Compostela, Spain
Hospital Alvaro Cunqueiro - Servicio de Oncologia
🇪🇸Vigo, Spain
Jilin Cancer Hospital - Oncology
🇨🇳Changchun, China
Hangzhou First People's Hospital
🇨🇳Hangzhou, China
Aichi Cancer Center Hospital - Dept of Respiratory Medicine
🇯🇵Nagoya-shi, Japan
University of Colorado Health - Memorial Hospital - Memorial Hospital
🇺🇸Colorado Springs, Colorado, United States
Hematology Oncology Associates
🇺🇸Fort Collins, Colorado, United States
Sanatorio Allende
🇦🇷Cordoba, Argentina
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Centro Polivalente de Asistencia e Inv. Clinica CER
🇦🇷San Juan, Argentina
Amphia Ziekenhuis - PARENT - Parent
🇳🇱Breda, Netherlands
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
AZ Delta
🇧🇪Roeselare, Belgium
Nippon Medical School Hospital - Dept of Respiratory Medicine
🇯🇵Bunkyo-ku, Japan
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital - Dept of Respiratory Medicine
🇯🇵Bunkyo-ku, Japan
National Cancer Center Hospital East - Dept of Respiratory Medicine
🇯🇵Kashiwa-shi, Japan
Kanagawa Cancer Center - Dept of Respiratory Medicine
🇯🇵Yokohama-shi, Japan
Jeroen Bosch Ziekenhuis
🇳🇱's Hertogenbosch, Netherlands
St. Antonius Ziekenhuis - Dept Pulmonology - Nieuwegein
🇳🇱Nieuwegein, Netherlands
CHU Mont-Godinne
🇧🇪Yvoir, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Saitama Medical University International Medical Center - Dept of Respiratory Medicine
🇯🇵Hidaka-shi, Japan
Kobe City Hospital Organization Kobe City Medical Center General Hospital - Dept of Respiratory Medicine
🇯🇵Kobe-shi, Japan
Shizuoka Cancer Center
🇯🇵Sunto-gun, Japan
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Osaka Medical Center for Cancer and Cardiovascular Diseases
🇯🇵Osaka-shi, Japan
Kindai University Hospital (13859)
🇯🇵Osakasayama-shi, Japan
St. Elisabeth Ziekenhuis - Parent
🇳🇱Tilburg, Netherlands
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine
🇯🇵Koto-ku, Japan
Kurume University Hospital - Dept of Lung Cancer Center
🇯🇵Kurume-shi, Japan
Martini ziekenhuis
🇳🇱Groningen, Netherlands
Meander Medisch Centrum - Dep of Pulmonology
🇳🇱Amersfoort, Netherlands
Ziekenhuis St. Jansdal
🇳🇱Harderwijk, Netherlands
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Chi Mei Medical Center, Liou Ying
🇨🇳Tainan, Taiwan
Clínica de Neoplasias Litoral Ltda.
🇧🇷Itajaí, Brazil
Hospital São Lucas da PUCRS
🇧🇷Porto Alegre, Brazil
Columbia University Medical Center
🇺🇸New York, New York, United States
South West Healthcare - South West Oncology
🇦🇺Warrnambool, Australia
University of California Irvine Medical Center
🇺🇸Orange, California, United States
Sylvester Comprehensive Cancer Center - University of Miami Health System
🇺🇸Miami, Florida, United States
UCLA Hematology Oncology - Main Site - 2020 Santa Monica
🇺🇸Santa Monica, California, United States
Holy Cross Hospital - Michael and Dianne Bienes CCC
🇺🇸Fort Lauderdale, Florida, United States
Sunshine Hospital
🇦🇺St Albans, Australia
UPMC Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Bendigo Hospital
🇦🇺Bendigo, Australia
St Vincent's Hospital Melbourne - PARENT
🇦🇺Fitzroy, Australia
Centre Hospitalier de la Côte Basque - Service de Pneumologie
🇫🇷Bayonne, France
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
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 Universitari Quiron Dexeus - Servicio de Oncologia Medica
🇪🇸Barcelona, Spain
Hospital Regional Universitario de Malaga
🇪🇸Málaga, Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Spain
Hospital Universitario Nuestra Señora de Valme - Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Macarena - Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocio - Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
🇪🇸Valencia, Spain
Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
🇪🇸Valencia, Spain
Clinica Universidad de Navarra (MAD) - Oncology Service
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre - 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