Safety Study of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors

A Phase 1/2a 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

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2014-002605-38-NO

Enrollment

2000

Registered

2016-05-11

Start date

Unknown

Completion date

Unknown

Last updated

2024-05-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neoplasms by site MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10073071 Term: Hepatocellular carcinoma System Organ Class:

Interventions

Product Name: Anti-LAG-3 -10mL VIAL Product Code: BMS-986016 Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: relatlimab Current Sponsor code: BMS986016 Other descriptive name

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: •For Dose escalation: subjects with cervical, ovarian, bladder and CRC, head and neck, gastric and hepatocellular cancer naive to immunooncology 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-4. •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 subjects in 1st line cohorts. •ECOG performance status of 0 to 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) Are the trial subjects under 18? yes Number of subjects for this age range: 2 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1140 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 840

Exclusion criteria

Exclusion criteria: - Primary 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

Design outcomes

Primary

Measure	Time frame
Main Objective: Part A+B+A1:to assess safety,tolerability,DLTs,MTD of BMS986016 alone &in combo with nivo (advanced solid tumors); to gather preliminary efficacy information of BMS986016 alone Part C:to further establish safety&tolerability of BMS986016 + nivo administered sequentially; to investigate the preliminary efficacy of BMS986016 in combo with nivo as measured by ORR, DCR,DOR (multiple tumor types) Part D: to assess safety&tolerability of more convenient dosing regimen;Part D1-Q2W: to demonstrate preliminary clinical evidence of the treatment effect,measured by ORR,as determined by BICR using RECIST v1.1 (advanced melanoma);Part D1-Q4W: to confirm with Q4W dosing of BMS986016 160 mg in combo with nivo480 mg,the safety&efficacy of the Q2W dosing of BMS986016 80 mg in combo with nivo 240mg (advanced melanoma) Part E: to demonstrate that 480 mg BMS986016 +480 mg nivo Q4W provides significantly greater clin benefit (increased ORR) vs 160mg BMS 986016+480 mg nivoQ4W dose (melanoma);Secondary Objective: -To characterize PK of BMS986016 alone and with nivo -To investigate preliminary ORR and/or DCR of BMS986016 alone and with nivo in subjects with advanced solid tumors(A,B,Dose Esc) -To characterize immunogenicity of BMS986016 alone and with nivo -To assess effect of BMS986016 alone & with nivo on QTc(A,B) -To evaluate DOR, DCR, PFS rates at pre-specified time points based on BICR assessments using RECISTv1.1 in advanced melanoma subjects i)with, i)with a lack, i)regardless LAG-3 expression(D1, D2) -To evaluate ORR, DCR, DOR, PFS rates at pre-specified time points based on Investigator assessments using RECISTv1.1 in advanced melanoma subjects i)with, i)with a lack, i)regardless LAG-3 expression(D1,D2) -To assess the 1Y and 2Y landmark OS in advanced melanoma subjects(D1, D2) -To assess safety and tolerability of more convenient dosing regimen in advanced melanoma subjects(D2) -To evaluate clinical benefit of 480mg BMS986016 + 480mg nivo Q4W using DOR in melanoma	—

Measure

Time frame

Main Objective: Part A+B+A1:to assess safety,tolerability,DLTs,MTD of BMS986016 alone &in combo with nivo (advanced solid tumors); to gather preliminary efficacy information of BMS986016 alone Part C:to further establish safety&tolerability of BMS986016 + nivo administered sequentially; to investigate the preliminary efficacy of BMS986016 in combo with nivo as measured by ORR, DCR,DOR (multiple tumor types) Part D: to assess safety&tolerability of more convenient dosing regimen;Part D1-Q2W: to demonstrate preliminary clinical evidence of the treatment effect,measured by ORR,as determined by BICR using RECIST v1.1 (advanced melanoma);Part D1-Q4W: to confirm with Q4W dosing of BMS986016 160 mg in combo with nivo480 mg,the safety&efficacy of the Q2W dosing of BMS986016 80 mg in combo with nivo 240mg (advanced melanoma) Part E: to demonstrate that 480 mg BMS986016 +480 mg nivo Q4W provides significantly greater clin benefit (increased ORR) vs 160mg BMS 986016+480 mg nivoQ4W dose (melanoma);Secondary Objective: -To characterize PK of BMS986016 alone and with nivo -To investigate preliminary ORR and/or DCR of BMS986016 alone and with nivo in subjects with advanced solid tumors(A,B,Dose Esc) -To characterize immunogenicity of BMS986016 alone and with nivo -To assess effect of BMS986016 alone & with nivo on QTc(A,B) -To evaluate DOR, DCR, PFS rates at pre-specified time points based on BICR assessments using RECISTv1.1 in advanced melanoma subjects i)with, i)with a lack, i)regardless LAG-3 expression(D1, D2) -To evaluate ORR, DCR, DOR, PFS rates at pre-specified time points based on Investigator assessments using RECISTv1.1 in advanced melanoma subjects i)with, i)with a lack, i)regardless LAG-3 expression(D1,D2) -To assess the 1Y and 2Y landmark OS in advanced melanoma subjects(D1, D2) -To assess safety and tolerability of more convenient dosing regimen in advanced melanoma subjects(D2) -To evaluate clinical benefit of 480mg BMS986016 + 480mg nivo Q4W using DOR in melanoma

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Secondary

Measure	Time frame
Secondary end point(s): - Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab - Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab - Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab - Concentration at the end of a dosing interval (Ctau) [Eg: concentration at 336 hours] of BMS-986016 administered both alone and in combination with nivolumab - Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986016 administered both alone and in combination with nivolumab - Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab - Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab - Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff AUC) of BMS- 986016 administered both alone and in combination with nivolumab - Effective elimination half-life that explains the degree of Cmax accumulation observed (T-HALFeff Cmax) of BMS-986016 administered both alone and in combination with nivolumab - Accumulation index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986016 administered both alone and in combination with nivolumab - Cmax accumulation index; ratio of Cmax at steady state to Cmax after the first dose (AI_Cmax) of BMS-986016 administered both alone and in combination with nivolumab - Ctau accumulation index; ratio of Ctau at steady state to Ctau after the first dose (AI_Ctau) of BMS-986016 administered both alone and in combination with nivolumab - Degree of fluctuation (DF) or fluctuation index ([Cmax -Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab - Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all pa	—

Measure

Time frame

Secondary end point(s): - Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab - Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab - Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab - Concentration at the end of a dosing interval (Ctau) [Eg: concentration at 336 hours] of BMS-986016 administered both alone and in combination with nivolumab - Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986016 administered both alone and in combination with nivolumab - Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab - Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab - Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff AUC) of BMS- 986016 administered both alone and in combination with nivolumab - Effective elimination half-life that explains the degree of Cmax accumulation observed (T-HALFeff Cmax) of BMS-986016 administered both alone and in combination with nivolumab - Accumulation index; ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose (AI_AUC) of BMS-986016 administered both alone and in combination with nivolumab - Cmax accumulation index; ratio of Cmax at steady state to Cmax after the first dose (AI_Cmax) of BMS-986016 administered both alone and in combination with nivolumab - Ctau accumulation index; ratio of Ctau at steady state to Ctau after the first dose (AI_Ctau) of BMS-986016 administered both alone and in combination with nivolumab - Degree of fluctuation (DF) or fluctuation index ([Cmax -Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab - Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all pa

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Countries

Australia, Austria, Canada, Denmark, Finland, France, Germany, Italy, Japan, Netherlands, Norway, Spain, Switzerland, United Kingdom, United States

Contacts

Public ContactGCT-SU

Bristol-Myers Squibb International Corporation

clinical.trials@bms.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026