A Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety profile of relatlimab plus nivolumab in combination with platinum doublet chemotherapy (PDCT) and to determine if nivolumab plus relatlimab in combination with PDCT improves overall response rate (ORR) when compared to nivolumab plus PDCT in participants with previously untreated Stage IV or recurrent non-small cell lung cancer (NSCLC).

Official Title
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A Phase 2 Randomized Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC)

Conditions
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Non-small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Metastatic Non-small Cell Lung Cancer

Intervention / Treatment
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* Biological: Nivolumab
* Biological: Relatlimab
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Paclitaxel
* Drug: Nab-Paclitaxel
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed metastatic non-small cell lung cancer (NSCLC) of squamous (SQ) or non-squamous (NSQ) histology with Stage IV A/B (as defined by the 8th International Association for the Study of Lung Cancer Classification) or recurrent disease following multi-modal therapy for locally advanced disease Eastern Cooperative Oncology Group (ECOG) performance status (PS) of less than or equal to 1 at screening and confirmed prior to randomization Measurable disease by computed tomography (CT) or magnetic resonance resources (MRI) per response evaluation criteria in solid tumor version 1.1 (RECIST 1.1) criteria No prior systemic anti-cancer treatment (including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors) given as primary therapy for advanced or metastatic disease Exclusion Criteria: Participants with EGFR, ALK, ROS-1, or known B-rapidly accelerated fibrosarcoma proto-oncogene (BRAF V600E) mutations that are sensitive to available targeted therapy Untreated CNS metastases Leptomeningeal metastases (carcinomatous meningitis) Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to randomization (ie, participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before randomization and the participant has no evidence of disease) Prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-programmed death-ligand 2 (PD-L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol-defined inclusion/exclusion criteria apply

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: Part 1: Arm A (Nivolumab + Relatlimab Dose 1 + Platinum Doublet Chemotherapy (PDCT))<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>Biological: Relatlimab<br>* Specified dose on specified days<br>Drug: Carboplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Cisplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Paclitaxel<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Nab-Paclitaxel<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Pemetrexed<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>|
| Experimental: Part 1: Arm B (Nivolumab + Relatlimab Dose 2 + PDCT))<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>Biological: Relatlimab<br>* Specified dose on specified days<br>Drug: Carboplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Cisplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Paclitaxel<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Nab-Paclitaxel<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Pemetrexed<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>|
| Experimental: Part 2: Arm C (Nivolumab + Relatlimab Dose 2 + PDCT)<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>Biological: Relatlimab<br>* Specified dose on specified days<br>Drug: Carboplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Cisplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Paclitaxel<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Pemetrexed<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>|
| Active Comparator: Part 2: Arm D (Nivolumab + PDCT)<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>Drug: Carboplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Cisplatin<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Paclitaxel<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>Drug: Pemetrexed<br>* Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related adverse events (TRAEs) leading to discontinuation within 12 weeks after the first dose | Part 1 | Up to 10 months, from first participant's first dose | 
| Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent clinical review (BICR) | Part 2 | 10 months after randomization, up to 21 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of TRAEs leading to discontinuation | Part 1 | Up to 10 months, 30 days from participant's last dose | 
| Incidence of Adverse Events (AEs) | Part 1 | Up to 10 months, 30 days from participant's last dose | 
| Incidence of Serious Adverse Events (SAEs) | Part 1 | Up to 10 months, 30 days from participant's last dose | 
| Incidence of select Adverse Events (AEs) | Part 1 | Up to 10 months, 30 days from participant's last dose | 
| PFS per RECIST v1.1 by BICR | Part 2 | Up to approximately 3 years | 
| Overall response rate (ORR) per RECIST v1.1 by BICR | Part 2 | Up to approximately 2 years | 
| Duration of Response (DoR) per RECIST v1.1 by BICR | Part 2 | At 6 months, 12 months, and 18 months | 
| Incidence of Adverse Events (AEs) | Part 2 | Up to 21 months | 
| Incidence of Serious Adverse Events (SAEs) | Part 2 | Up to 21 months | 
| Incidence of Treatment Related Adverse Events (TRAEs) | Part 2 | Up to 21 months | 
| Incidence of Immune-mediated Adverse Events (IMAEs) | Part 2 | Up to 21 months | 
| Incidence of select Adverse Events (AEs) | Part 2 | Up to 21 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nivolumab, Stage IV Non-small Cell Lunch Cancer, Recurrent Non-small Cell Lung Cancer, Metastatic Non-small Cell Lung Cancer, Relatlimab, Chemotherapy