Safety Study of BMS-986015 (Anti-KIR) in Combination With Ipilimumab in Subjects With Selected Advanced Tumor

• Safety as measured by the rate of adverse events, and serious adverse events [ Time Frame: Up to a maximum of 1.4 years (treatment period) ] [ Designated as safety issue: Yes ]
• Safety as measured by the rate of adverse events, and serious adverse events [ Time Frame: 90 days (follow-up) ] [ Designated as safety issue: Yes ]

• Efficacy as measured by tumor assessment (per RECIST 1.1 and irRECIST 1.1) [ Time Frame: Up to 1.4 years (treatment) and 90 days (follow-up) ] [ Designated as safety issue: No ]

  Efficacy will be measured based on immune-related Response Evaluation Criteria for Solid Tumors (irRECIST) 1.1 and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using Best overall response (BOR), Objective response rate (ORR), Duration of Response (DOR), Progression-Free Survival Rate (PFSR)

  Efficacy will be measured on every 6-12 weeks while on treatment and approximately every 12 weeks during follow-up

• The maximum observed serum concentration (Cmax) of BMS-986015 and Ipilimumab [ Time Frame: Up to 17 time points in 18 months ] [ Designated as safety issue: Yes ]
• The time of maximum observed serum concentration (Tmax) of BMS-986015 and Ipilimumab [ Time Frame: Up to 17 time points in 18 months ] [ Designated as safety issue: Yes ]
• Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986015 and Ipilimumab [ Time Frame: Up to 17 time points in 18 months ] [ Designated as safety issue: Yes ]
• Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986015 and Ipilimumab [ Time Frame: Up to 17 time points in 18 months ] [ Designated as safety issue: Yes ]
• Apparent total body clearance (CL) of BMS-986015 and Ipilimumab [ Time Frame: Up to 17 time points in 18 months ] [ Designated as safety issue: Yes ]
• Apparent volume of distribution at steady state (Vss) of BMS-986015 and Ipilimumab [ Time Frame: Up to 17 time points in 18 months ] [ Designated as safety issue: Yes ]
• Serum half-life (T-HALF) of BMS-986015 and Ipilimumab [ Time Frame: Up to 17 time points in 18 months ] [ Designated as safety issue: Yes ]
• Trough observed serum concentration (Cmin) of BMS-986015 and Ipilimumab [ Time Frame: Up to 17 time points in 18 months ] [ Designated as safety issue: Yes ]
• Immunogenicity as measured by the incidence of Ipilimumab and anti-Killer cell immunoglobulin-like receptor (KIR) (BMS-986015) anti-drug antibodies (ADA) [ Time Frame: 9 time points in 18 months ] [ Designated as safety issue: Yes ]
• Immunohistochemistry on mandatory tumor biopsies based on measures of Tumor infiltrating lymphocyte (TIL) [ Time Frame: Baseline (Day 1) and at week 12 (Induction therapy) ] [ Designated as safety issue: No ]
• Immunohistochemistry on mandatory tumor biopsies based on Programmed Death Ligand 1 (PD-L1) [ Time Frame: Baseline (Day 1) and at week 12 (Induction therapy) ] [ Designated as safety issue: No ]
• Immunohistochemistry on mandatory tumor biopsies based on Human leukocyte antigen (HLA) Class I expression [ Time Frame: Baseline (Day 1) and at week 12 (Induction therapy) ] [ Designated as safety issue: No ]

To assess the safety and tolerability, characterize the dose-limiting toxicities (DLTs), and identify the maximally tolerated dose (MTD) of BMS-986015 given in combination with ipilimumab in subjects with select advanced (metastatic and/or unresectable) solid tumors.

• Drug: BMS-986015
  Other Name: Anti-KIR
• Drug: Ipilimumab
  Other Name: BMS-734016

• Experimental: Arm 1: BMS-986015 + Ipilimumab

  BMS-986015 0.1, 0.3, 1 or 3 mg/kg and Ipilimumab 3 or 10 mg/kg Solution by Intravenous every 3 weeks in the induction phase for a total of 4 doses for 23 weeks and in maintenance phase every 12 weeks for an additional 4 doses for 37 weeks

  • Dose Escalation
  Interventions:

  • Drug: BMS-986015
  • Drug: Ipilimumab
• Experimental: Arm 2: BMS-986015 + Ipilimumab

  BMS-986015 and Ipilimumab Solution by Intravenous dose selected during dose escalation every 3 weeks in the induction phase for a total of 4 doses for 23 weeks and in maintenance phase every 12 weeks for an additional 4 doses for 37 weeks

  • Cohort Expansion
  Interventions:

  • Drug: BMS-986015
  • Drug: Ipilimumab

Inclusion Criteria:

• Histologic confirmation of one of the following solid tumors that is advanced (unresectable or metastatic) for dose escalation or cohort expansion:Non-Small Cell Lung Cancer (NSCLC), Castrate Resistant Prostate Cancer (CRPC), Melanoma (MEL)
• At least one measurable lesion at baseline by Computed tomography (CT) or Magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Biopsies: Subjects in the melanoma cohort must have at least 1 tumor site that can be biopsied at acceptable clinical risk
• Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
• Estimated life expectancy of ≥ 12 weeks
• White blood cell (WBC) ≥2000/μL, Neutrophils ≥1500/μL, Platelets ≥ 100x1000/μL, Hemoglobin ≥ 8.5 g/dL, creatinine ≤ 1.5 X upper limit of normal (ULN) mL/min, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 3x ULN

Exclusion Criteria:

• Participation in any prior clinical study with BMS-936558 or ipilimumab that has overall survival listed as a primary/co-primary endpoint
• Subjects with known or suspected brain metastasis
• Subjects with active autoimmune disease, uncontrolled or significant cardiovascular disease
• Prior therapy with anti- Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) antibody or anti- Killer cell immunoglobulin-like receptor (KIR) antibody