A Phase I/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Nivolumab
- Conditions
- Neoplasms by Site
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 1482
- Locations
- 109
- Primary Endpoint
- Number of Participants With Adverse Events, Deaths and Clinically Relevant Laboratory Abnormalities
- Status
- Completed
- Last Updated
- 26 days ago
Overview
Brief Summary
The purpose of the study is to assess the safety, tolerability and effectiveness of experimental medication BMS-986016 administered alone and in combination with nivolumab in patients with solid tumors that have spread and/or cannot be removed by surgery.
The following tumor types are included in this study:
Non-Small Cell Lung Cancer (NSCLC), gastric cancer, hepatocellular carcinoma, renal cell carcinoma, bladder cancer, squamous cell carcinoma of the head and neck, and melanoma, that have NOT previously been treated with immunotherapy. NSCLC and melanoma that HAVE previously been treated with immunotherapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For Dose escalation: subjects with cervical, ovarian, bladder and colorectal cancer (CRC), head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and 1st line/2nd line NSCLC; Renal Cell Carcinoma naive to IO; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with or without anti-CTLA-
- •For Dose Expansion: all of the above in escalation except for cervical, ovarian, and CRC
- •Progressed, or been intolerant to, at least one standard treatment regimen, except for participants in 1st line cohorts.
- •ECOG performance status between 0 and 2
- •At least 1 lesion with measurable disease at baseline
- •Availability of an existing tumor biopsy sample (and consent to allow pre-treatment tumor biopsy)
Exclusion Criteria
- •Primary central nervous system (CNS) tumors or solid tumors with CNS metastases as the only site of active disease
- •Autoimmune disease
- •Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
- •Uncontrolled CNS metastases
- •Other protocol defined inclusion/exclusion criteria could apply
Arms & Interventions
Relatlimab + Nivolumab
Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days
Intervention: Nivolumab
BMS-986213
Relatlimab (BMS-986016) + Nivolumab (BMS-936558)
Intervention: BMS-986213
Relatlimab + Nivolumab
Relatlimab (BMS-986016) + Nivolumab (BMS-936558) specified dose on specified days
Intervention: Relatlimab
Relatlimab
Relatlimab (BMS-986016) specified dose on specified days
Intervention: Relatlimab
Outcomes
Primary Outcomes
Number of Participants With Adverse Events, Deaths and Clinically Relevant Laboratory Abnormalities
Time Frame: From first dose and within 135 days after last dose of study therapy (Up to approximately 82 months)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. SAEs is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization; results significant disability; or is a congenital anomaly/birth defect.
Part C, D1, D2, E - Objective Response Rate Per BICR
Time Frame: From first dose (Day 1) and up to 97 months
ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. 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. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the 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 5 mm.
Part C, D1, D2, E - Disease Control Rate (DCR) Per BICR
Time Frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)
Disease Control Rate (DCR) (as per Recists v1.1) is defined as the percentage of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments 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. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the 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 5 mm.
Part C, D1, D2, E - Duration of Response (DOR) Per BICR
Time Frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)
DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method. 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. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Part D1: Number of Participants With Adverse Events in the Broad Scope Standardized MedDRA (SMQ) Anaphylactic Reaction Occurring Within 2 Days of Any Doses of Study Therapy
Time Frame: From first dose and within 2 days of first dose of study therapy
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Part C, D1, D2, E - Objective Response Rate Per BICR
Time Frame: From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months)
ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method. 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. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the 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 5 mm.
Secondary Outcomes
- Part C, D1 and D2: Progression-Free Survival (PFS) Rate Per BICR(Up to 12 months)
- Part C, D1 and D2: Progression-Free Survival (PFS) Rate Per Investigator(Up to 12 months)
- Part A/A1, B, CTotal Body Clearance (CLT) of BMS-986016 (Relatlimab)(Day 1 of Cycle 3 (Each cycle consist of 28 days).)
- Part C, D1 and D2: Progression-Free Survival (PFS) Rate up to 12 Months Per BICR(Up to 12 months)
- Part D1 and D2: Overall Survival (OS) at 12 and 24 Months(At 12 and 24 months after first dose)
- Part C, D1, D2, E - Objective Response Rate Per Investigator(From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months))
- Part C, D1, D2, E - Disease Control Rate (DCR) Per Investigator(From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months))
- Part C, D1, D2, E - Duration of Response (DOR) Per Investigator(From first dose to the date of first objectively documented progression, per RECIST v1.1, or death due to any cause, whichever occurred first (up to approximately 127 months))
- Part C, D1 and D2: Progression-Free Survival (PFS) Rate up to 12 Months Per Investigator(Up to 12 months)
- Maximum Observed Concentration (Cmax) of BMS-986016 (Relatlimab)(Day 1 of Cycle 1 and 3)
- Time to Maximum Observed Concentration (Tmax) of BMS-986016 (Relatlimab)(Day 1 of Cycle 1 and 3 (Each cycle consist of 28 days).)
- Area Under the Concentration-time Curve in One Dosing Interval (AUCtau) of BMS-986016 (Relatlimab)(Day 1 of Cycle 1 and 3 (Each cycle consist of 28 days).)
- Part A/A1, B, C, D1, D2 and E: Trough Observed Concentration (Ctrough) of BMS-986016 (Relatlimab)(Day 1 of Cycle 3 (Each cycle consist of 28 days))
- Part A/A1, B, C Total Body Clearance (CLT) of BMS-986016 (Relatlimab)(Day 1 of Cycle 3 (Each cycle consist of 28 days).)
- Part A/A1, B, C AUC Accumulation Index AI_AUC of BMS-986016 (Relatlimab)(Day 1 of Cycle 3 (Each cycle consist of 28 days))
- Number of Participants With Positive Anti Drug Antibodies(predose, and 4-hour post-dose of relatlimab on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle consist of 28 days))
- Part A, A/A1, and B: Number of Participants With Clinically Relevant QT Prolongation(predose, and 4-hour post-dose of relatlimab on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle consist of 28 days))