A Phase I Study of an Anti-KIR Antibody in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors
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Purpose
The purpose of this study is to assess the safety and tolerability of BMS-986015 given in combination with BMS-936558 and to identify dose limiting toxicities (DLTs) and the maximally tolerated dose (MTD) of the combination, in subjects with advanced (metastatic and/or unresectable) solid tumors
| Condition | Intervention | Phase |
|---|---|---|
|
CANCER,NOS |
Drug: BMS-986015 (ANTI-KIR) Drug: BMS-936558 (ANTI-PD1) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 1 Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-KIR (BMS-986015) Administered in Combination With Anti-PD-1 (BMS-936558) in Advanced Refractory Solid Tumors |
- Safety and tolerability of BMS-986015 given in combination with BMS-936558 as measured by incidence of adverse events [ Time Frame: Approximately up to 27 months ] [ Designated as safety issue: Yes ]
- Safety and tolerability of BMS-986015 given in combination with BMS-936558 as measured by incidence of clinical laboratory test abnormalities including hematology and serum chemistry, and thyroid panel abnormalities [ Time Frame: Approximately up to 27 months ] [ Designated as safety issue: Yes ]
- Anti-tumor activity will be based on Best overall response (BOR), Objective response rate (ORR), Duration of Response (DOR) and Progression-Free Survival Rate (PFSR) using Immune-related RECIST (irRECIST) and RECIST v1.1 [ Time Frame: Approximately up to 27 months ] [ Designated as safety issue: No ]
Every 8 weeks during the Treatment Period (Cycle 1 Day 1 through Cycle 12 Day 56), and once during clinical follow-up
RECIST = Response Evaluation Criteria In Solid Tumors
- Maximum observed serum concentration (Cmax) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Time of maximum observed serum concentration (Tmax) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Trough observed serum concentration (Ctrough) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Clearance (CL) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Volume of distribution at steady state (Vss) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Half-life (t1/2) of BMS-986015 derived from serum concentration versus time [ Time Frame: 13 time points up to 27 months ] [ Designated as safety issue: Yes ]
- End of infusion of BMS-936558 derived from serum concentration versus time [ Time Frame: 9 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Trough observed concentration (Cmin) of BMS-936558 derived from serum concentration versus time [ Time Frame: 9 time points up to 27 months ] [ Designated as safety issue: Yes ]
- Immunogenicity of BMS-986015 and BMS-936558 measured by occurrence of specific anti-drug antibodies to BMS-986015 and BMS-936558 [ Time Frame: Approximately up to 27 months ] [ Designated as safety issue: Yes ]
- Measures of Tumor infiltrating lymphocyte(s) (TILs), Programmed Death Ligand-1 (PD-L1) and Human Leukocyte Antigen (HLA) Class I expression using immunohistochemistry [ Time Frame: Screening (Day -28 to -1) and Day 112 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 150 |
| Study Start Date: | October 2012 |
| Estimated Study Completion Date: | August 2015 |
| Estimated Primary Completion Date: | August 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm 1: Dose Escalation (BMS-986015 0.1mg/kg+BMS-936558 3mg/kg)
BMS-986015 0.1 mg/kg Solution, Intravenous, every 4 weeks, 8 - 96 weeks depending on response BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, 8 - 96 weeks depending on response |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
|
Experimental: Arm 2: Dose Escalation (BMS-986015 0.3mg/kg+BMS-936558 3mg/kg)
BMS-986015 0.3 mg/kg Solution, Intravenous, every 4 weeks, 8 - 96 weeks depending on response BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, 8 - 96 weeks depending on response |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
|
Experimental: Arm 3: Dose Escalation (BMS-986015 1mg/kg+BMS-936558 3mg/kg)
BMS-986015 1 mg/kg Solution, Intravenous, every 4 weeks, 8 - 96 weeks depending on response BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, 8 - 96 weeks depending on response |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
|
Experimental: Arm 4: Dose Escalation (BMS-986015 3mg/kg+BMS-936558 3mg/kg)
BMS-986015 3 mg/kg Solution, Intravenous, every 4 weeks, 8 - 96 weeks depending on response BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, 8 - 96 weeks depending on response |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
|
Experimental: Arm 5: Cohort Expansion (NSCLC - squamous histology)
BMS-986015 MTD (to be determined from dose escalation) or an alternate dose, if recommended by the investigators and the sponsor, Solution, Intravenous, every 4 weeks, until unacceptable toxicity BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, until unacceptable toxicity NSCLC = Non small cell lung cancer |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
|
Experimental: Arm 6: Cohort Expansion (NSCLC - non-squamous histology)
BMS-986015 MTD (to be determined from dose escalation) or an alternate dose, if recommended by the investigators and the sponsor, Solution, Intravenous, every 4 weeks, until unacceptable toxicity BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, until unacceptable toxicity |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
|
Experimental: Arm 7: Cohort Expansion (RCC with a clear cell component)
BMS-986015 MTD (to be determined from dose escalation) or an alternate dose, if recommended by the investigators and the sponsor, Solution, Intravenous, every 4 weeks, until unacceptable toxicity BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, until unacceptable toxicity RCC = Renal Cell Carcinoma |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
|
Experimental: Arm 8: Cohort Expansion (Melanoma)
BMS-986015 MTD (to be determined from dose escalation) or an alternate dose, if recommended by the investigators and the sponsor, Solution, Intravenous, every 4 weeks, until unacceptable toxicity BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, until unacceptable toxicity |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
|
Experimental: Arm 9: Cohort Expansion (Colorectal Cancer)
BMS-986015 MTD (to be determined from dose escalation) or an alternate dose, if recommended by the investigators and the sponsor, Solution, Intravenous, every 4 weeks, until unacceptable toxicity BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, until unacceptable toxicity |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
|
Experimental: Arm 10: Cohort Expansion (Serous Ovarian Carcinoma)
BMS-986015 MTD (to be determined from dose escalation) or an alternate dose, if recommended by the investigators and the sponsor, Solution, Intravenous, every 4 weeks, until unacceptable toxicity BMS-936558 3 mg/kg Solution, Intravenous, every 2 weeks, until unacceptable toxicity |
Drug: BMS-986015 (ANTI-KIR)
KIR = Killer-cell Immunoglobulin-like Receptors
Other Name: IPH-2102
Drug: BMS-936558 (ANTI-PD1)
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- During dose escalation, subjects with advanced solid tumors (except for primary CNS metastases) that have progressed following at least one standard regimen
- During cohort expansion, subjects with non small cell lung cancer, melanoma, renal cell carcinoma, melanoma, colorectal, and ovarian cancer that have received at least one and no more than 5 prior treatment regimens
- Subjects must have measurable disease
- Subject must consent to provide previously collected tumor tissue
- Women and men ≥ 18 years of age with performance status of 0 or 1
- At least 4 weeks since any previous treatment for cancer
Exclusion Criteria:
- Prior therapy with an immune cell modulating antibody except for anti-Cytotoxic T Lymphocyte Antigen 4 (CTLA4)
- Active or chronic autoimmune diseases
- Uncontrolled or significant cardiovascular disease
- Chronic hepatitis
- Active infection
- Active Central nervous system (CNS) metastases
Contacts and Locations| 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. |
| United States, Illinois | |
| University Of Chicago Medical Center | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| Contact: Thomas F Gajewski, Site 0005 773-834-1942 | |
| United States, Maryland | |
| Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins | Recruiting |
| Baltimore, Maryland, United States, 21287 | |
| Contact: William Sharfman, Site 0002 410-502-2540 | |
| United States, Massachusetts | |
| Local Institution | Not yet recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Site 0006 | |
| Local Institution | Not yet recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Site 0007 | |
| Dana Farber Cancer Institute | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: F. Stephen Hodi, Site 0001 617-632-6191 | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Ctr | Recruiting |
| New York, New York, United States, 10065 | |
| Contact: Neil Segal, Site 0003 646-888-3359 | |
| United States, Oregon | |
| Providence Portland Med Ctr | Recruiting |
| Portland, Oregon, United States, 97213 | |
| Contact: Rachel Sanborn, Site 0004 503-215-6080 | |
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT01714739 History of Changes |
| Other Study ID Numbers: | CA223-001 |
| Study First Received: | October 24, 2012 |
| Last Updated: | April 4, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
ClinicalTrials.gov processed this record on May 21, 2013