A Safety Study of Lirilumab in Combination With Nivolumab or in Combination With Nivolumab and Ipilimumab in Advanced and/or Metastatic Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine whether lirilumab in combination with nivolumab or in combination with nivolumab and ipilimumab is safe in the treatment of advanced and/or metastatic solid tumors

Official Title
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A Phase 1 Study of the Safety and Pharmacokinetics of Anti-KIR Monoclonal Antibody (Lirilumab, BMS-986015) in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab,BMS-936558) or in Combination With Nivolumab and Anti-CTLA-4 Monoclonal Antibody (Ipilimumab, BMS-734016) in Advanced and/or Metastatic Solid Tumors

Conditions
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Advanced Cancer

Intervention / Treatment
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* Biological: Lirilumab
* Biological: Nivolumab
* Biological: Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Participants must have histologic or cytologic confirmation of a solid malignancy that is advanced (metastatic and/or unresectable) Presence of at least 1 lesion with measurable disease as defined by response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) criteria for response assessment The Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Participants with untreated central nervous system (CNS) metastases Participants with an active, known, or suspected autoimmune disease Uncontrolled or significant cardiovascular disease Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part One Combination Therapy<br>Lirilumab and Nivolumab | Biological: Lirilumab<br>* Specified dose on specified days<br>* Other names: BMS-986015;Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Part 2 Combination Therapy<br>Lirilumab, Nivolumab and Ipilimumab | Biological: Lirilumab<br>* Specified dose on specified days<br>* Other names: BMS-986015;Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: Yervoy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity (DLT) | To assess the safety and tolerability of lirilumab in combination with nivolumab | Up to two years | 
| Incidence of adverse events (AEs) | To assess the safety and tolerability of lirilumab in combination with nivolumab | Up to two years | 
| Incidence of serious adverse events (SAEs) | To assess the safety and tolerability of lirilumab in combination with nivolumab | Up to two years | 
| Incidence of death | To assess the safety and tolerability of lirilumab in combination with nivolumab | Up to two years | 
| Frequency of laboratory test toxicity grade shifting from baseline | To assess the safety and tolerability of lirilumab in combination with nivolumab | Up to two years | 
| Incidence of AEs leading to discontinuation | To assess the safety and tolerability of lirilumab in combination with nivolumab | Up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity (DLT) | To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab | Up to two years | 
| Incidence of adverse events (AEs) | To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab | Up to two years | 
| Incidence of serious adverse events (SAEs) | To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab | Up to two years | 
| Incidence of death | To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab | Up to two years | 
| Frequency of laboratory test toxicity grade shifting from baseline | To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab | Up to two years | 
| Maximum serum observed concentration (Cmax) | To characterize the Pharmacokinetic (PK) of lirilumab given in combination with nivolumab | Up to two years | 
| Time of maximum observed serum concentration (Tmax) | To characterize the PK of lirilumab given in combination with nivolumab | Up to two years | 
| Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration [AUC(0-T)] | To characterize the PK of lirilumab given in combination with nivolumab | Up to two years | 
| Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] | To characterize the PK of lirilumab given in combination with nivolumab | Up to two years | 
| Trough observed serum concentration (Ctrough) | To characterize the PK of lirilumab given in combination with nivolumab | Up to two years | 
| Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] | To characterize the PK of lirilumab given in combination with nivolumab | Up to two years | 
| Clearance (CL) | To characterize the PK and immunogenicity of lirilumab given in combination with nivolumab | Up to two years | 
| Volume of distribution at steady state (Vss) | To characterize the PK of lirilumab given in combination with nivolumab | Up to two years | 
| Ratio of an exposure measure at steady-state to that after the first dose (AI) | To characterize the PK of lirilumab given in combination with nivolumab | Up to two years | 
| Half-life (T-HALF) | To characterize the PK of lirilumab given in combination with nivolumab | Up to two years | 
| Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (T-HALF eff) | To characterize the PK of lirilumab given in combination with nivolumab | Up to two years | 
| Best overall response (BOR) | To assess the preliminary anti-tumor activity | Up to two years | 
| Duration of response (DOR) | To assess the preliminary anti-tumor activity | Up to two years | 
| Incidence of anti-drug antibody (ADA) | To characterize immunogenicity | Up to two years | 
| Incidence of AEs leading to discontinuation | To assess the safety and tolerability of lirilumab in combination with nivolumab and ipilimumab | Up to two years | 
| Maximum serum observed concentration (Cmax) | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Time of maximum observed serum concentration (Tmax) | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration [AUC(0-T)] | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Trough observed serum concentration (Ctrough) | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Clearance (CL) | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Volume of distribution at steady state (Vss) | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Ratio of an exposure measure at steady-state to that after the first dose (AI) | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Half-life (T-HALF) | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years | 
| Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (T-HALF eff) | To characterize the PK of lirilumab given in combination with nivolumab and ipilimumab | Up to two years |