Clinical trial NCT01750580: Safety Study of BMS-986015 (Anti-KIR) in Combination With Ipilimumab in Subjects With Selected Advanced Tumor
Official title: A Phase 1 Study of BMS-986015, an Anti-KIR Monoclonal Antibody, Administered With Ipilimumab, an Anti-CTLA4 Monoclonal Antibody, in Subjects With Select Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: CANCER, NOS
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-12-17
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

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
* Normal thyroid function or be on stable hormone supplementation

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
* Grade 2 neuropathy

Primary outcomes:
measure: Safety as measured by the rate of adverse events, and serious adverse events
timeFrame: Approximately 510 days
Secondary outcomes:
measure: Efficacy as measured by tumor assessment
timeFrame: Assessed from the start of treatment (ay 1) to the end of treatment (week 60) and for 90 days in follow-up
measure: The maximum observed serum concentration (Cmax) of BMS-986015 and Ipilimumab
timeFrame: up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2. (EOI is end of infusion, EOT is end of treatment
measure: The time of maximum observed serum concentration (Tmax) of BMS-986015 and Ipilimumab
timeFrame: up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2
measure: Area under the serum concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986015 and Ipilimumab
timeFrame: up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2
measure: Area under the serum concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986015 and Ipilimumab
timeFrame: up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, EOT, follow-up 1 and follow-up 2
measure: Apparent total body clearance (CL) of BMS-986015 and Ipilimumab
timeFrame: up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2
measure: Apparent volume of distribution at steady state (Vss) of BMS-986015 and Ipilimumab
timeFrame: up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2
measure: Serum half-life (T-HALF) of BMS-986015 and Ipilimumab
timeFrame: up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2
measure: Trough observed serum concentration (Cmin) of BMS-986015 and Ipilimumab
timeFrame: up to 18 timepoints following each dose during Weeks 1, (0h, EOI and 24h), 2, 3, 4, 10, (0h, EOI and 24h), 11, 13, 24, (0h and EOI), 36, 48, 60, follow-up 1 and follow-up 2
measure: Immunogenicity as measured by the incidence of Ipilimumab and anti-Killer cell immunoglobulin-like receptor (KIR) (BMS-986015) anti-drug antibodies (ADA)
timeFrame: up to 11 timepoints during Weeks 1, 3, 4, 10, 13, 24, 36,48, 60, follow-up 1 and follow-up 2
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University Of Minnesota
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Ctr
state: New York
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: