A Study of BMS-986315 and Nivolumab in Combination With Chemotherapy in Participants With First-line Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC)

A Randomized, Double-blind, Phase 2 Study of BMS-986315 and Nivolumab in Combination With Chemotherapy Versus Nivolumab in Combination With Chemotherapy as First-line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC)

The purpose of this study is to evaluate the efficacy and safety of BMS-986315 plus nivolumab in combination with platinum-based doublet chemotherapy (PDCT) versus nivolumab in combination with PDCT in the first-line treatment of Stage IV or recurrent non-small cell lung cancer (NSCLC).

Study Overview

• Status: Terminated
• Conditions: NSCLC
• Intervention / Treatment: Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Nivolumab; Drug: BMS-986315

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Local Institution - 0013
    • Tweed Heads, New South Wales, Australia, 2485
      • Local Institution - 0021
  • Western Australia
    • Joondalup, Western Australia, Australia, 6027
      • Local Institution - 0032
• United States
  • California
    • Glendale, California, United States, 37219
      • Local Institution - 0038
  • Florida
    • Clermont, Florida, United States, 34711
      • Local Institution - 0044
    • Orange City, Florida, United States, 32763
      • Local Institution - 0040
  • Idaho
    • Boise, Idaho, United States, 83706
      • Local Institution - 0058
  • Texas
    • Houston, Texas, United States, 77090
      • Local Institution - 0049

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have NSCLC with Stage IV or recurrent disease following multimodal therapy for locally advanced disease.
• Study treatment must be first-line therapy for Stage IV or recurrent disease.
• Participants in all parts of the study must have:
• measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1. (RECIST v1.1)
• an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• a life expectancy of at least 3 months at the time of first dose

Exclusion Criteria:

• Untreated symptomatic central nervous system metastases
• Participants with epidermal growth factor receptor (EGFR)/ALK receptor tyrosine kinase (ALK)/ROS proto-oncogene 1 (ROS1)/neurotrophic tyrosine receptor kinase (NTRK)/MET proto-oncogene (MET)/B-Raf proto-oncogene (BRAF)/RET proto-oncogene (RET) mutations amenable to targeted therapies
• Participants with any known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results

Note: Other protocol-defined inclusion/exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: BMS-986315 Dose Level (DL) 1 + Nivolumab + Histology-based PDCT	Drug: Carboplatin; Specified dose on specified days; Drug: Cisplatin; Specified dose on specified days; Drug: Paclitaxel; Specified dose on specified days; Drug: Pemetrexed; Specified dose on specified days; Drug: BMS-986315; Specified dose on specified days; Other Names: Anti-NKG2A
Experimental: Part 1: BMS-986315 DL 2 + Nivolumab + Histology-based PDCT	Drug: Carboplatin; Specified dose on specified days; Drug: Cisplatin; Specified dose on specified days; Drug: Paclitaxel; Specified dose on specified days; Drug: Pemetrexed; Specified dose on specified days; Drug: BMS-986315; Specified dose on specified days; Other Names: Anti-NKG2A
Active Comparator: Part 2: Nivolumab + Histology-based PDCT	Drug: Carboplatin; Specified dose on specified days; Drug: Cisplatin; Specified dose on specified days; Drug: Paclitaxel; Specified dose on specified days; Drug: Pemetrexed; Specified dose on specified days; Drug: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo
Experimental: Part 2: BMS-986315 DL 2 + Nivolumab + Histology-based PDCT	Drug: Carboplatin; Specified dose on specified days; Drug: Cisplatin; Specified dose on specified days; Drug: Paclitaxel; Specified dose on specified days; Drug: Pemetrexed; Specified dose on specified days; Drug: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Drug: BMS-986315; Specified dose on specified days; Other Names: Anti-NKG2A
Experimental: Part 2: BMS-986315 DL 1 + Nivolumab + Histology-based PDCT	Drug: Carboplatin; Specified dose on specified days; Drug: Cisplatin; Specified dose on specified days; Drug: Paclitaxel; Specified dose on specified days; Drug: Pemetrexed; Specified dose on specified days; Drug: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Opdivo; Drug: BMS-986315; Specified dose on specified days; Other Names: Anti-NKG2A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) for Part 1	An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention.	From first dose through 100 days following last dose of study treatment (assessed for approximately 7 months)
Number of Participants With Treatment Related Adverse Events (TRAEs) for Part 1	An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention.	From first dose through 100 days following last dose of study treatment (assessed for approximately 7 months)
Number of Participants With Serious Adverse Events (SAEs) for Part 1	Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization.	From first dose through 100 days following last dose of study treatment (assessed for approximately 7 months)
Number of Participants With Adverse Events (AEs) Meeting Protocol-defined Dose-limiting Toxicity (DLT) Criteria for Part 1	Dose-Limiting Toxicities (DLTs) are treatment effects serious enough to prevent dose increase. Severity grades: 1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening, 5=Death; Grade 2 uveitis or eye pain not improving or require systemic treatment; Grade 2 pneumonitis or interstitial lung disease >14 days; Grade ≥ 3 uveitis, episcleritis, iritis, pneumonitis, bronchospasm or neurologic toxicity; Grade 3 colitis not responding >48 hours; Hepatic abnormalities without liver metastases: serum transaminases (AST/ALT) >5x & ≤ 8xULN for >2weeks, AST/ALT >8xULN regardless of duration, total bilirubin >3xULN, or concurrent AST/ALT >3xULN & total bilirubin >2xULN; Hepatic abnormalities with liver metastases: AST/ALT >8x & ≤10xULN for >2 weeks, AST/ALT >10xULN regardless of duration, total bilirubin > 3xULN, or concurrent AST/ALT >8xULN & total bilirubin >2xULN; Grade 3 (hypersensitivity reaction not resolving to Grade 1 in 6 hours; fatigue >7 days; nausea, vomiting, or diarrhea >72 hours)	From first dose (Cycle 1 Day 1) up to day 28
Number of Participants With Adverse Events (AEs) Leading to Discontinuation for Part 1	An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention.	From first dose through 100 days following last dose of study treatment (assessed for approximately 7 months)
Number of Participants Who Died in Part 1	Number of participants who died during the study	From first dose through 100 days following last dose of study treatment (assessed for approximately 7 months)
Objective Response Rate (ORR) for Part 2	Objective response rate (ORR) is defined as the number of participants who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), based on blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. No participants were enrolled in Part 2 due to the study termination; therefore, no data were collected for this endpoint.	From randomization until the date of first objectively documented progression or start of subsequent therapy whichever occurred first (planned for up to approximately 5 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) for Part 2	Progression free survival is defined as the time between the date of randomization and the first date of documented progression, per blinded independent central review (BICR) assessments using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), or death due to any cause, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm (Note: The appearance of 1or more new lesions is also considered progression). No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	From randomization until the date of first objectively documented progression or death due to any cause, whichever occurred first (planned for up to approximately 5 years)
Number of Participants With Adverse Events (AEs) for Part 2	An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention. No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	Up to 100 days after discontinuation of study treatment
Number of Participants With Treatment Related Adverse Events (TRAEs) for Part 2	An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention. No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	Up to 100 days after discontinuation of study treatment
Number of Participants With Serious Adverse Events (SAEs) for Part 2	Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization. No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	Up to 100 days after discontinuation of study treatment
Number of Participants With Adverse Events (AEs) Meeting Protocol-defined Dose-limiting Toxicity (DLT) Criteria for Part 2	Dose-Limiting Toxicities (DLTs) are treatment effects serious enough to prevent dose increase. Severity grades: 1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening, 5=Death; Grade 2 uveitis or eye pain not improving or require systemic treatment; Grade 2 pneumonitis or interstitial lung disease >14 days; Grade ≥ 3 uveitis, episcleritis, iritis, pneumonitis, bronchospasm or neurologic toxicity; Grade 3 colitis not responding >48 hours; Hepatic abnormalities without liver metastases: serum transaminases (AST/ALT) >5x & ≤ 8xULN for >2weeks, AST/ALT >8xULN regardless of duration, total bilirubin >3xULN, or concurrent AST/ALT >3xULN & total bilirubin >2xULN; Hepatic abnormalities with liver metastases: AST/ALT >8x & ≤10xULN for >2 weeks, AST/ALT >10xULN regardless of duration, total bilirubin > 3xULN, or concurrent AST/ALT >8xULN & total bilirubin >2xULN; Grade 3 (hypersensitivity reaction not resolving to Grade 1 in 6 hours; fatigue >7 days; nausea, vomiting, or diarrhea >72 hours)	Up to 100 days after discontinuation of study treatment
Number of Participants With Adverse Events (AEs) Leading to Discontinuation for Part 2	An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention. No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	Up to 100 days after discontinuation of study treatment
Number of Participants Who Died in Part 2	Number of participants who died during the study No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	Up to 100 days after discontinuation of study treatment
Duration of Response (DoR) for Part 2	Duration of response is defined as the time between the date of first documented response (CR or PR) that is subsequently confirmed, to the date of the 1st objectively documented tumor progression as determined by BICR (per RECIST 1.1), or death due to any cause, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm (Note: The appearance of 1or more new lesions is also considered progression).	From randomization until the date of first objectively documented progression or death due to any cause, whichever occurred first (planned for up to approximately 5 years)
Time to Objective Response (TTR) for Part 2	Time to response (TTR) assessed by BICR is defined as the time between the date of randomization and the first confirmed documented response (CR or PR) per RECIST 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	From randomization until the date of first objectively documented progression or death due to any cause, whichever occurred first (planned for up to approximately 5 years)
Disease Control Rate (DCR) for Part 2	Disease control rate (DCR) is defined as the number of participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments (using RECIST 1.1) divided by the number of all randomized participants. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	From randomization until the date of first objectively documented progression or death due to any cause, whichever occurred first (planned for up to approximately 5 years)
Maximum Observed Serum Concentration (Cmax) for Part 2	Cmax is the maximum observed serum concentration. No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 (Each Cycle is of 21 Days)
Time of Maximum Observed Concentration (Tmax) for Part 2	Tmax is the time of maximum observed serum concentration. No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	C1D1, C1D2, C1D4, C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C5D2, C5D4, C5D8, C5D15, Day 1 of every 4 cycles from cycle 6 (up to 2 years); at 30 and 100 days post last dose (Each Cycle is of 21 Days)
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] for Part 2	AUC (0-T) is the area under the serum concentration-time curve from time zero to time of last quantifiable concentration. No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	C1D1, C1D2, C1D4, C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C5D2, C5D4, C5D8, C5D15, Day 1 of every 4 cycles from cycle 6 (up to 2 years); at 30 and 100 days post last dose (Each Cycle is of 21 Days)
Number of Participants With Anti-drug Antibodies (ADA) to BMS-986315 for Part 2	Number of Participants with Anti-drug Antibodies (ADA) to BMS-986315 No participants were enrolled in Part 2 due to the study's termination; therefore, no data were collected for this endpoint.	Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Day 1 of every 4 cycles from cycle 6 (up to 2 years); at 30 and 100 days post last dose (Each Cycle is of 21 Days)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Actual): August 8, 2024
• Study Completion (Actual): August 8, 2024

Study Registration Dates

• First Submitted: October 17, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; Nivolumab; Pharmacokinetics; Lung cancer; Platinum doublet chemotherapy; BMS-986315
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Nivolumab; Pemetrexed; Carboplatin; Paclitaxel
• Other Study ID Numbers: CA047-1009; 2022-503007-22 (EudraCT Number); U1111-1282-5699 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myers Squibb's data sharing policy and process can be found at: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No