An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 8 April 2024
• Main ID: NCT01968109
• Date of registration: 25/09/2013
• Prospective Registration: Yes
• Primary sponsor: Bristol-Myers Squibb
• Public title: An Investigational Immuno-therapy Study to Assess the Safety, Tolerability and Effectiveness of Anti-LAG-3 With and Without Anti-PD-1 in the Treatment of Solid Tumors
• Scientific title: 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
• Date of first enrolment: November 5, 2013
• Target sample size: 1499
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01968109
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

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

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion 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-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
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



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Neoplasms by Site

Intervention(s)

Biological: BMS-986213

Biological: Nivolumab

Biological: Relatlimab

Primary Outcome(s)

Proportion of participants with laboratory abnormalities in blood serum [Time Frame: Approximately Up to 3 years]

Number of AEs in the Broad Scope MedDRA Anaphylactic Reaction SMQ [Time Frame: Approximately 3 years]

Proportion of Deaths [Time Frame: Approximately Up to 3 years]

Duration of response (DOR) [Time Frame: Approximately 3 years]

Proportion of participants with Adverse Events (AEs) [Time Frame: Approximately Up to 3 years]

Proportion of participants with laboratory abnormalities in blood [Time Frame: Approximately Up to 3 years]

Proportion of participants with laboratory abnormalities in urine [Time Frame: Approximately Up to 3 years]

Proportion of participants with Serious Adverse Events (SAEs) [Time Frame: Approximately Up to 3 years]

Objective response rate (ORR) [Time Frame: Approximately 3 years]

Proportion of participants with AEs leading to discontinuation of treatment [Time Frame: Approximately up to 3 years]

Disease control rate (DCR) [Time Frame: Approximately 3 years]

Secondary Outcome(s)

Best overall response (BOR) [Time Frame: Approximately 3 years]

Maximum observed serum concentration (Cmax) of BMS-986016 administered both alone and in combination with nivolumab [Time Frame: Approximately 2.3 years]

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 [Time Frame: Approximately 2.3 years]

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 [Time Frame: Approximately 2.3 years]

Progression-free survival (PFS) rates [Time Frame: Up to approximately 3 years]

QTc interval from centrally read electrocardiograms (ECGs) [Time Frame: Approximately 2.3 years]

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 [Time Frame: Approximately 2.3 years]

Number of AEs in the Narrow Scope MedDRA Anaphylactic Reaction SMQ [Time Frame: Approximately 3 years]

ORR [Time Frame: Approximately 3 years]

DCR [Time Frame: Approximately 3 years]

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 [Time Frame: Approximately 2.3 years]

Degree of fluctuation (DF) or fluctuation index ([Cmax - Ctau]/Css,avg]) of BMS-986016 administered both alone and in combination with nivolumab [Time Frame: Approximately 2.3 years]

Volume of distribution at steady state (Vss) of BMS-986016 administered both alone and in combination with nivolumab [Time Frame: Approximately 2.3 years]

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 [Time Frame: Approximately 2.3 years]

Duration of response (DOR) [Time Frame: Approximately 3 years]

Effective elimination half-life that explains the degree of area under the concentration-time curve (AUC) accumulation observed (T-HALFeff AUC) of BMS-986016 administered both alone and in combination with nivolumab [Time Frame: Approximately 2.3 years]

Overall survival (OS) [Time Frame: Approximately 2 years]

Time of maximum observed serum concentration (Tmax) of BMS-986016 administered both alone and in combination with nivolumab [Time Frame: Approximately 2.3 years]

Total body clearance (CLT) of BMS-986016 administered both alone and in combination with nivolumab [Time Frame: Approximately 2.3 years]

Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986016 administered both alone and in combination with nivolumab [Time Frame: Approximately 2.3 years]

Immunogenicity measured by anti-drug antibody (ADA) for BMS-986016 (all participants) and nivolumab [Time Frame: Approximately 2.3 years]

Trough observed serum concentration (Ctrough) of BMS-986016 administered both alone and in combination with nivolumab [Time Frame: Approximately 2.3 years]

Secondary ID(s)

CA224-020

2023-508067-70

Source(s) of Monetary Support

Please refer to primary and secondary sponsors