Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03840902
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : May 29, 2020
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 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 : April 16, 2019
Estimated Primary Completion Date : March 4, 2024
Estimated Study Completion Date : January 26, 2028

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

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]).




Primary Outcome Measures :
  1. Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) Assessed by Independent Review Committee (IRC) [ Time Frame: Time from first dose up to 59 Months ]

Secondary Outcome Measures :
  1. Occurrence of Treatment Emergent Adverse Events (TEAEs) and Treatment-related AEs [ Time Frame: Baseline up to 8.8 years ]
  2. Overall Survival [ Time Frame: Baseline up to 8.8 years ]
  3. Changes from Baseline in Diffusing Capacity of Lung for Carbon Monoxide (DLCO) [ Time Frame: Baseline up to 14 months ]
  4. Programmed death-ligand 1 (PD-L1) Expression in Tumors Assessed with Immunohistochemistry (IHC) and Association with Efficacy [ Time Frame: Baseline up to 8.8 years ]
  5. Objective Response According to RECIST 1.1 Assessed by IRC [ Time Frame: Baseline up to 8.8 years ]
  6. Duration of Response According to RECIST 1.1 [ Time Frame: Baseline up to 8.8 years ]
  7. Immunogenicity of M7824 as Measured by Antidrug Antibody (ADA) Assays [ Time Frame: Baseline up to 8.8 years ]
  8. Concentration Immediately Before Next Dosing (Ctrough) [ Time Frame: Baseline up to 14 months ]
  9. Concentration Immediately at End of Infusion (Ceoi) [ Time Frame: Baseline up to 14 months ]
  10. Changes from Baseline in High-resolution Computed Tomography (HRCT) [ Time Frame: Baseline up to 14 months ]
  11. Changes from Baseline in Forced Expiratory Volume in one Second (FEV1) [ Time Frame: Baseline up to 14 months ]
  12. Changes from Baseline in Forced Vital Capacity (FVC) [ Time Frame: Baseline up to 14 months ]
  13. Changes from Baseline in 6-minutes Walking Test [ Time Frame: Baseline up to 14 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03840902


Contacts
Layout table for location contacts
Contact: US Medical Information 888-275-7376 service@emdgroup.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com

Locations
Layout table for location information
United States, Florida
Lynn Cancer Institute Center Recruiting
Boca Raton, Florida, United States, 33486
Contact       hrichter@brrh.com   
Principal Investigator: Harold Richter         
United States, Indiana
American Health Network of Indiana, LLC Recruiting
Indianapolis, Indiana, United States, 46202
Contact       sridhar_boll@ahni.com   
Principal Investigator: Sridhar R Bolla         
United States, New York
Hematology Oncology Center of Nyack Hospital Recruiting
Nyack, New York, United States, 10960
Contact       lees@montefiorenyack.org   
Principal Investigator: Sung Ho Lee         
United States, North Carolina
FirstHealth of the Carolinas, Inc. Recruiting
Pinehurst, North Carolina, United States, 28374
Contact       ckuzma@firsthealth.org   
Principal Investigator: Charles S Kuzma         
Japan
National Cancer Center Hospital East - Dept of Respiratory Medicine Recruiting
Kashiwa-shi, Japan, 277-8577
Contact       yzenken@cick.jp   
Principal Investigator: Yoshitaka Zenke         
Kobe City Hospital Organization Kobe City Medical Center General Hospital - Dept of Respiratory Medicine Recruiting
Kobe-shi, Japan, 650-0047
Contact       ktomii@kcho.jp   
Principal Investigator: Keisuke Tomii         
Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine Recruiting
Koto-ku, Japan, 135-8550
Contact       mnishio@jfcr.or.jp   
Principal Investigator: Makoto Nishio         
Kurume University Hospital - Dept of Lung Cancer Center Recruiting
Kurume-shi, Japan, 830-0011
Contact       ishii_hidenobu@med.kurume-u.ac.jp   
Principal Investigator: Hidenobu Ishii         
Kindai University Hospital (13859) Recruiting
Osakasayama-shi, Japan, 589-8511
Contact       hidet31@med.kindai.ac.jp   
Principal Investigator: Hidetoshi Hayashi         
Kanagawa Cancer Center - Dept of Respiratory Medicine Recruiting
Yokohama-shi, Japan, 241-8515
Contact       katote@kcch.jp   
Principal Investigator: Terufumi Kato         
Spain
Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia Recruiting
Madrid, Spain, 28050
Contact       bjimenez@hmhospitales.com   
Principal Investigator: Beatriz Jimenez Munarriz         
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
Layout table for investigator information
Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany
Additional Information:
Layout table for additonal information
Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT03840902    
Other Study ID Numbers: MS200647_0005
2018-003265-34 ( EudraCT Number )
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients 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 https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Non-small Cell Lung Cancer
Bintrafusp alfa (proposed INN)
M7824
Durvalumab
Stage III
INTR@PID LUNG 005
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Etoposide
Carboplatin
Pemetrexed
Durvalumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Immunological