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)

• ClinicalTrials.gov Identifier: NCT04623775
• Recruitment Status: Active, not recruiting
• First Posted: November 10, 2020
• Last Update Posted: October 5, 2023
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: November 5, 2020
• First Posted Date: November 10, 2020
• Last Update Posted Date: October 5, 2023
• Actual Study Start Date: February 17, 2021
• Estimated Primary Completion Date: May 28, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 20, 2022)

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

Original Primary Outcome Measures (submitted: November 5, 2020)

• Treatment-related adverse events (TRAEs) leading to discontinuation within 12 weeks after the first dose [ Time Frame: Up to 10 months, from first participant's first dose ]
  Part 1
• Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent clinical review (BICR) [ Time Frame: 10 months after randomization, up to 21 months ]
  Part 2

Current Secondary Outcome Measures (submitted: August 20, 2022)

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

Original Secondary Outcome Measures (submitted: November 5, 2020)

• Incidence of TRAEs leading to discontinuation [ Time Frame: Up to 10 months, 30 days from participant's last dose ]
  Part 1
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: Up to 10 months, 30 days from participant's last dose ]
  Part 1
• Incidence of select Adverse Events (AEs) [ Time Frame: Up to 10 months, 30 days from participant's last dose ]
  Part 1
• PFS per RECIST v1.1 by BICR in biomarker subgroups [ Time Frame: Until progression, up to 21 months ]
  Part 2
• Overall response rate (ORR) per RECIST v1.1 by BICR [ Time Frame: Up to 21 months ]
  Part 2
• Incidence of Serious Adverse Events (SAEs) [ Time Frame: Up to 21 months ]
  Part 2
• Incidence of select Adverse Events (AEs) [ Time Frame: Up to 21 months ]
  Part 2

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: 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)
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment

Condition

• Non-small Cell Lung Cancer
• Recurrent Non-small Cell Lung Cancer
• Metastatic Non-small Cell Lung Cancer

Intervention

• Biological: Nivolumab
  Specified dose on specified days
• Biological: Relatlimab
  Specified dose on specified days
• Drug: Carboplatin
  Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.
• Drug: Cisplatin
  Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.
• Drug: Paclitaxel
  Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.
• Drug: Nab-Paclitaxel
  Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.
• Drug: Pemetrexed
  Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.

Study Arms

• Experimental: Part 1: Arm A (Nivolumab + Relatlimab Dose 1 + Platinum Doublet Chemotherapy (PDCT))
  Interventions:

  • Biological: Nivolumab
  • Biological: Relatlimab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Nab-Paclitaxel
  • Drug: Pemetrexed
• Experimental: Part 1: Arm B (Nivolumab + Relatlimab Dose 2 + PDCT))
  Interventions:

  • Biological: Nivolumab
  • Biological: Relatlimab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Nab-Paclitaxel
  • Drug: Pemetrexed
• Experimental: Part 2: Arm C (Nivolumab + Relatlimab Dose 2 + PDCT)
  Interventions:

  • Biological: Nivolumab
  • Biological: Relatlimab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Pemetrexed
• Active Comparator: Part 2: Arm D (Nivolumab + PDCT)
  Interventions:

  • Biological: Nivolumab
  • Drug: Carboplatin
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Pemetrexed

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: August 20, 2022): 420
• Original Estimated Enrollment (submitted: November 5, 2020): 520
• Estimated Study Completion Date: September 16, 2025
• Estimated Primary Completion Date: May 28, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Chile, France, Germany, Ireland, Italy, Mexico, Netherlands, Poland, Romania, Russian Federation, Spain, Switzerland, United Kingdom, United States
• Removed Location Countries: Canada, New Zealand, Turkey

Administrative Information

• NCT Number: NCT04623775
• Other Study ID Numbers: CA224-104; 2020-004026-31 ( EudraCT Number ); U1111-1256-8115 ( Registry Identifier: WHO )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bristol-Myers Squibb
• Original Responsible Party: Same as current
• Current Study Sponsor: Bristol-Myers Squibb
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: October 2023