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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: M7824
* Drug: Placebo
* Drug: Durvalumab
* Drug: Etoposide
* Drug: Pemetrexed
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Cisplatin
* Radiation: Intensity Modulated Radiation Therapy (IMRT)


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: cCRT plus M7824 followed by M7824<br>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<br>* 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.<br>Drug: Etoposide<br>* 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.<br>Drug: Pemetrexed<br>* 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.<br>Drug: Carboplatin<br>* 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.<br>Drug: Paclitaxel<br>* 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.<br>Drug: Cisplatin<br>* 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.<br>Radiation: Intensity Modulated Radiation Therapy (IMRT)<br>* Participants will receive IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).<br>|
| Active Comparator: Arm 2: cCRT plus placebo followed by durvalumab<br>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<br>* 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.<br>Drug: Durvalumab<br>* 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.<br>Drug: Etoposide<br>* 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.<br>Drug: Pemetrexed<br>* 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.<br>Drug: Carboplatin<br>* 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.<br>Drug: Paclitaxel<br>* 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.<br>Drug: Cisplatin<br>* 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.<br>Radiation: Intensity Modulated Radiation Therapy (IMRT)<br>* Participants will receive IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small Cell Lung Cancer, Bintrafusp alfa (proposed INN), M7824, Durvalumab, Stage III, INTR@PID LUNG 005