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

Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03840902
• Other study ID #: MS200647_0005
• Secondary ID: 2018-003265-34
• Status: Terminated
• Phase: Phase 2
• Start date: April 16, 2019
• Est. completion date: February 17, 2023

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 153
• Est. completion date: February 17, 2023
• Est. primary completion date: February 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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]).

Locations

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

Sponsors (2)

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

Countries where clinical trial is conducted

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

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 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	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)
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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)

External Links

•   Trial Awareness and Transparency website