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

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03840902

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

168

Enrollment

104

Locations

Arms

48.8

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is 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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: M7824 Drug: Placebo Drug: Durvalumab Drug: Etoposide Drug: Pemetrexed Drug: Carboplatin Drug: Paclitaxel Drug: Cisplatin Radiation: Intensity Modulated Radiation Therapy (IMRT)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

168 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 16, 2019

Anticipated Primary Completion Date :

May 9, 2023

Anticipated Study Completion Date :

May 9, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: cCRT plus M7824 followed by M7824 Participants will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 will receive cisplatin 50 mg/m^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants will receive cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT. Radiation: Intensity Modulated Radiation Therapy (IMRT) Participants will receive IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).
Active Comparator: Arm 2: cCRT plus placebo followed by durvalumab Participants will receive 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: Placebo Participants will receive 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 will receive 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. Drug: Etoposide Participants will receive 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 will receive 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 will receive 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 will receive 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 will receive cisplatin 50 mg/m^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants will receive cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT. Radiation: Intensity Modulated Radiation Therapy (IMRT) Participants will receive IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).

Arm

Intervention/Treatment

Experimental: Arm 1: cCRT plus M7824 followed by M7824

Participants will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 will receive 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 will receive cisplatin 50 mg/m^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants will receive cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT.

Radiation: Intensity Modulated Radiation Therapy (IMRT)

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

Active Comparator: Arm 2: cCRT plus placebo followed by durvalumab

Participants will receive 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: Placebo

Participants will receive 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 will receive 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.

Drug: Etoposide

Participants will receive 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 will receive 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 will receive 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 will receive 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

Radiation: Intensity Modulated Radiation Therapy (IMRT)

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

Outcome Measures

Primary Outcome Measures

Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Investigator [Time from randomization to final assessment at 3 years and 6 months]

Secondary Outcome Measures

Occurrence of Treatment Emergent Adverse Events (TEAEs) and Treatment-related AEs [Time from randomization to final assessment at 3 years and 6 months]
Overall Survival [Time from randomization to final assessment at 3 years and 6 months]
Objective response according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Time from randomization to final assessment at 3 years and 6 months]
Duration of Response Assessed by Investigator [Time from randomization to final assessment at 3 years and 6 months]
Pharmacokinetics Profile of M7824 in Terms of Concentration Immediately at End of Infusion (Ceoi) and Concentration Immediately Before Next Dosing (Ctrough) [Time from randomization to final assessment at 17 months]
Immunogenicity of M7824 as Measured by Antidrug Antibody (ADA) Assays [Time from randomization to final assessment at 17 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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