INCMGA00012 in Combination With Chemoradiation in Participants With Stage III Non-Small Cell Lung Cancer (POD1UM-301)

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of INCMGA00012 in combination with chemoradiation therapy (CRT) in participants with unresectable, Stage III non-small cell lung cancer (NSCLC). The study will randomize approximately 360 participants in a 2:1 ratio into the INCMGA00012 in combination with CRT followed by consolidation therapy with INCMGA00012 treatment group and placebo in combination with CRT followed by consolidation therapy with placebo treatment group.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of INCMGA00012, an Anti-PD-1 Antibody, in Combination With Chemoradiation in Participants With Unresectable, Stage III Non-Small Cell Lung Cancer (POD1UM-301)

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Retifanlimab
* Drug: Placebo
* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Etoposide
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed NSCLC that is locally advanced and unresectable. Adequate tumor sample from fresh biopsy or archival tissue block must be available. Evaluable disease per RECIST v1.1. Eastern Cooperative Oncology Group performance status 0 to 1. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: Receipt of cancer treatment for this malignancy, including but not limited to radiation therapy, investigational agents, chemotherapy, and immunotherapy for disease under consideration. Recent major surgery within 4 weeks before entry into the study. Any medical contraindication to platinum-based doublet chemotherapy. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic consolidation doses of corticosteroids (> 10 mg/day of prednisone or equivalent). Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids). Mixed small cell and NSCLC histology. Evidence of interstitial lung disease or active noninfectious pneumonitis. Participants who are HIV-positive. History of organ transplant, including allogeneic stem cell transplantation.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemoradiation therapy + INCMGA00012<br> | Drug: Retifanlimab<br>* INCMGA00012 administered intravenously every 3 weeks on Day 1 of each 21-day cycle for 4 cycles, followed by a consolidation part of INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to12 cycles.<br>* Other names: INCMGA00012;Drug: Pemetrexed<br>* Pemetrexed administered intravenously every 3 weeks on Day 1 of each cycle with either carboplatin or cisplatin (nonsquamous NSCLC only) for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Drug: Cisplatin<br>* Cisplatin administered intravenously every 3 weeks on Day 1 of each cycle with either etoposide or pemetrexed (nonsquamous NSCLC only) for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Drug: Carboplatin<br>* Carboplatin administered intravenously every 3 weeks on Day 1 of each cycle with either pemetrexed (nonsquamous NSCLC only) or paclitaxel for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Drug: Paclitaxel<br>* Paclitaxel administered intravenously every 3 weeks on Days 1, 8, and 15 of each cycle with carboplatin for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Drug: Etoposide<br>* Etoposide administered intravenously every 3 weeks on Days 1-3 of each cycle with cisplatin for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Radiation: Radiotherapy<br>* Total dose of 60 Gy ± 10% (54 to 66 Gy) in 2 Gy daily fractions.<br>|
| Active Comparator: Chemoradiation therapy + Placebo<br> | Drug: Placebo<br>* Placebo administered intravenously every 3 weeks on Day 1 of each 21-day cycle for 4 cycles, followed by a consolidation part of placebo administered intravenously on Day 1 of each 28-day cycle for up to 12 cycles.<br>Drug: Pemetrexed<br>* Pemetrexed administered intravenously every 3 weeks on Day 1 of each cycle with either carboplatin or cisplatin (nonsquamous NSCLC only) for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Drug: Cisplatin<br>* Cisplatin administered intravenously every 3 weeks on Day 1 of each cycle with either etoposide or pemetrexed (nonsquamous NSCLC only) for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Drug: Carboplatin<br>* Carboplatin administered intravenously every 3 weeks on Day 1 of each cycle with either pemetrexed (nonsquamous NSCLC only) or paclitaxel for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Drug: Paclitaxel<br>* Paclitaxel administered intravenously every 3 weeks on Days 1, 8, and 15 of each cycle with carboplatin for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Drug: Etoposide<br>* Etoposide administered intravenously every 3 weeks on Days 1-3 of each cycle with cisplatin for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).<br>Radiation: Radiotherapy<br>* Total dose of 60 Gy ± 10% (54 to 66 Gy) in 2 Gy daily fractions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Defined as the time from randomization until disease progression, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by blinded independent central review (BICR), or death due to any cause. | Up to approximately 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Defined as the time from randomization until death due to any cause. | Up to approximately 3 years. | 
| Objective response rate (ORR) | Defined as the percentage of participants having a complete response or partial response per RECIST v1.1 based on BICR. | Up to approximately 3 years. | 
| Duration of response (DOR) | Defined as the time from the first documented response (complete response or partial response) according to RECIST v1.1 until disease progression or death due to any cause. | Up to approximately 3 years. | 
| Number of treatment-emergent adverse events | Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study treatment. | Up to approximately 3 years. | 
| Cmax of INCMGA00012. | Maximum observed plasma or serum concentration. | Cycle 1 Day 1, Cycle 2 Day 1 and Consolidation Cycle 1 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, and Cycle 12 Day 1, up to approximately 18 months. | 
| tmax of INCMGA00012. | Time to maximum concentration. | Cycle 1 Day 1, Cycle 2 Day 1 and Consolidation Cycle 1 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, and Cycle 12 Day 1, up to approximately 18 months. | 
| Cmin of INCMGA00012. | Minimum observed plasma or serum concentration over the dose interval. | Cycle 1 Day 1, Cycle 2 Day 1 and Consolidation Cycle 1 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, and Cycle 12 Day 1, up to approximately 18 months. | 
| AUC0-t of INCMGA00012. | Area under the plasma or serum concentration curve. | Cycle 1 Day 1, Cycle 2 Day 1 and Consolidation Cycle 1 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, and Cycle 12 Day 1, up to approximately 18 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, unresectable, Stage III, PD-1, PD-L1