Platinum-Based Chemotherapy With/Without INCMGA00012, an Anti-PD-1 Antibody, in Non-Small Cell Lung Cancer

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 platinum-based chemotherapy with or without INCMGA00012 in participants with metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC).

Official Title
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A Randomized, Double Blind, Phase 3 Study of Platinum-Based Chemotherapy With or Without INCMGA00012 in First-Line Metastatic Squamous and Nonsquamous Non-Small Cell Lung Cancer (POD1UM-304)

Conditions
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Metastatic Squamous Non-Small Cell Lung Cancer, Metastatic Nonsquamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Retifanlimab
* Drug: Placebo
* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: nab-Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed NSCLC (either nonsquamous or squamous) that is Stage IV (AJCC v8). No prior systemic treatment for the advanced/metastatic NSCLC Able to provide a formalin-fixed archival tumor tissue sample during screening, or a fresh tumor biopsy Measurable disease per RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy of at least 3 months. Willingness to avoid pregnancy or fathering children. Adequate organ function as indicated by protocol-specified laboratory values. - Has been fully vaccinated against SARS-CoV-2 or is willing and able to be fully vaccinated against SARS-CoV-2 during the study by starting the vaccination process during screening. Exclusion Criteria: Clinically significant cardiac disease within 6 months of start of study treatment. Any major surgery within 3 weeks of the first dose of study treatment. Thoracic radiation therapy of > 30 Gy within 6 months of the first dose of study treatment. History of peripheral neuropathy ≥ Grade 2 CTCAE v5 for participants who may receive cisplatin, paclitaxel, or nab-paclitaxel. Untreated central nervous system metastases and/or carcinomatous meningitis. Evidence or history of interstitial lung disease or noninfectious pneumonitis that required systemic steroids. Active infection requiring systemic therapy or active tuberculosis. Note: If required by country or local regulations to be tested for COVID-19 during screening, a participant should be excluded if they have a positive test result for SARS CoV-2 infection until both the retesting result is negative and clinical recovery is obtained. Superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers. Has contraindications to chemotherapy agents used in the study. Has an active autoimmune disease that has required systemic treatment in past 2 years. Is receiving systemic antibiotics or steroid therapy ≤ 7 days prior to the first dose of study treatment. Has received a live vaccine within 30 days before the first dose of study treatment (and until 90 days after last dose of study drug). Note: While based on approved SARS-CoV-2 vaccines available worldwide, many vaccines are not live (mRNA and adenovirus vaccines do not contain live virus), if a live vaccine against SARS-CoV-2 is the only available option, prior consultation with the medical monitor should be obtained. • Has known active HBV or HCV (testing must be performed to determine eligibility)

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: INCMGA00012 + chemotherapy (nonsquamous NSCLC)<br>INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression. | Drug: Retifanlimab<br>* INCMGA00012 administered intravenously every 3 weeks on Day 1 of each cycle for up to 35 cycles.<br>* Other names: INCMGA00012;Drug: Pemetrexed<br>* Pemetrexed administered intravenously every 3 weeks on Day 1 of each cycle.<br>Drug: Cisplatin<br>* Cisplatin administered intravenously every 3 weeks on Day 1 of each cycle for 4 cycles.<br>Drug: Carboplatin<br>* Carboplatin administered intravenously every 3 weeks on Day 1 of each cycle for 4 cycles.<br>|
| Active Comparator: Placebo + chemotherapy (nonsquamous NSCLC)<br>Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. | Drug: Placebo<br>* Placebo administered intravenously every 3 weeks on Day 1 of each cycle for up to 35 cycles.<br>Drug: Pemetrexed<br>* Pemetrexed administered intravenously every 3 weeks on Day 1 of each cycle.<br>Drug: Cisplatin<br>* Cisplatin administered intravenously every 3 weeks on Day 1 of each cycle for 4 cycles.<br>Drug: Carboplatin<br>* Carboplatin administered intravenously every 3 weeks on Day 1 of each cycle for 4 cycles.<br>|
| Experimental: INCMGA00012 + chemotherapy (squamous NSCLC)<br>INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression. | Drug: Retifanlimab<br>* INCMGA00012 administered intravenously every 3 weeks on Day 1 of each cycle for up to 35 cycles.<br>* Other names: INCMGA00012;Drug: Carboplatin<br>* Carboplatin administered intravenously every 3 weeks on Day 1 of each cycle for 4 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel administered intravenously every 3 weeks on Day 1 of each cycle for 4 cycles.<br>Drug: nab-Paclitaxel<br>* nab-Paclitaxel administered intravenously every 3 weeks on Days 1, 8, and 15 of each cycle for 4 cycles.<br>|
| Active Comparator: Placebo + chemotherapy (squamous NSCLC)<br>Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. | Drug: Placebo<br>* Placebo administered intravenously every 3 weeks on Day 1 of each cycle for up to 35 cycles.<br>Drug: Carboplatin<br>* Carboplatin administered intravenously every 3 weeks on Day 1 of each cycle for 4 cycles.<br>Drug: Paclitaxel<br>* Paclitaxel administered intravenously every 3 weeks on Day 1 of each cycle for 4 cycles.<br>Drug: nab-Paclitaxel<br>* nab-Paclitaxel administered intravenously every 3 weeks on Days 1, 8, and 15 of each cycle for 4 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Defined as the time from randomization until death due to any cause. | Approximately 4.5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Defined as the time from randomization until disease progression by 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. | Approximately 4.5 years | 
| Objective response rate (ORR) | Defined as the proportion of participants who have a confirmed complete response or partial response per RECIST v1.1 based on BICR. | Approximately 4.5 years. | 
| Duration of response (DOR) | Defined as the time from the earliest date of documented response until earliest date of disease progression (per RECIST v1.1 based on BICR) or death from any cause, whichever comes first. | Approximately 4.5 years. | 
| Number of treatment-emergent adverse events | Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment up to 90 days after last dose of study treatment. | Approximately 4.5 years. | 
| Cmax of INCMGA00012 when administered with chemotherapy | Maximum observed plasma or serum concentration. | Approximately 4.5 years. | 
| AUC of INCMGA00012 when administered with chemotherapy | Area under the plasma or serum concentration curve. | Up to approximately 4.5 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic, non-small cell lung cancer, nonsquamous, squamous, PD-1, PD-L1