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 Tumours

Official 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 Tumours

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 tumours that have spread and/or cannot be removed by surgery. The following tumour 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.

Trial Description

Primary Outcome:

• Proportion of subjects with Adverse Events (AEs)
• Proportion of subjects with Serious Adverse Events (SAEs)
• Proportion of Deaths
• Proportion of subjects with laboratory abnormalities
• Objective response rate (ORR)
• Disease control rate (DCR)
• Duration of response (DOR)
• Proportion of participants with AEs meeting acute safety criteria
• Proportion of subjects with AEs leading to discontinuation of treatment

• 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 area under the concentration-time curve (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 subjects) and nivolumab
• QTc interval from centrally read electrocardiograms (ECGs)
• Best overall response (BOR)
• ORR
• DCR
• Duration of response (DOR)
• Progression-free survival (PFS)
• Overall survival (OS)

View this trial on ClinicalTrials.gov