Text Size

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

This study is currently recruiting participants.
Verified December 2012 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01750580
First received: December 6, 2012
Last updated: March 28, 2013
Last verified: December 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
CANCER, NOS
 Drug: BMS-986015
Drug: Ipilimumab
 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer
Drug Information available for: Ipilimumab
U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 125
Study Start Date: January 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
 Drug: BMS-986015
Other Name: Anti-KIR
Drug: Ipilimumab
Other Name: BMS-734016
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
 Drug: BMS-986015
Other Name: Anti-KIR
Drug: Ipilimumab
Other Name: BMS-734016

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01750580

Contacts
Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations
United States, Florida
Local Institution Not yet recruiting
Tampa, Florida, United States, 33612
Contact: Site 0008            
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Geoffrey Gibney, Site 0001     813-745-1676        
United States, Massachusetts
Local Institution Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Site 0002            
Local Institution Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Site 0010            
Local Institution Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Site 0009            
United States, Minnesota
Local Institution Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Site 0006            
United States, New York
Local Institution Not yet recruiting
New York, New York, United States, 10065
Contact: Site 0003            
United States, Ohio
Local Institution Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Site 0007            
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Jeffrey Infante, Site 0005     615-524-4546        
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
BMS Clinical Trial Information  This link exits the ClinicalTrials.gov site
BMS clinical trial educational resource  This link exits the ClinicalTrials.gov site
Investigator Inquiry form  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01750580     History of Changes
Other Study ID Numbers: CA223-002
Study First Received: December 6, 2012
Last Updated: March 28, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013