Safety and Efficacy Study of BMS-908662 in Combination With Ipilimumab in Subjects With Advanced Melanoma

Study Overview
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Brief Summary
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The purpose of the study is to identify a safe and tolerable dose of BMS-908662 in combination with ipilimumab; and then to evaluate the anti-tumor response to BMS-908662 when administered in combination with ipilimumab.

Official Title
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A Phase 1 Study of a RAF Inhibitor (BMS-908662) Administered in Combination With Immunotherapy (Ipilimumab) in Subjects With Unresectable Stage III or Stage IV Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: BMS-908662
* Drug: BMS-908662
* Drug: Ipilimumab
* Drug: Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion: Male and female subjects ≥ 18 years of age with a histologic or cytologic diagnosis of Stage III or Stage IV (unresectable) melanoma Enrollment to cohort expansion will be limited to only those subjects whose tumors demonstrate the B-Raf V600E mutation ECOG ≤ 1 Adequate organ & marrow function Exclusion: Uncontrolled or significant cardiovascular disease Cohort expansion: Prior therapy with a RAF inhibitor

Ages Eligible for Study
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Minimum Age: 18 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: BMS-908662 or Ipilimumab (A)<br> | Drug: BMS-908662<br>* Capsules, Oral, escalating doses starting at 25 mg, Q 12 h daily, Continuously<br>Drug: Ipilimumab<br>* Vial, IV, escalating doses starting at 3 mg/kg, Once every 3 weeks for 6 weeks, then once every 12 weeks, Continuously<br>|
| Experimental: BMS-908662 or Ipilimumab (B)<br> | Drug: BMS-908662<br>* Capsules, Oral, escalating doses starting at 25 mg Q 12 h daily for 3 weeks with 3 weeks interval for 4 cycles, then Q12 h daily for 3 weeks every 12 weeks, Continuously<br>Drug: Ipilimumab<br>* Vial, IV, escalating doses starting at 3 mg/kg, Once every 6 weeks for 4 cycles, then once every 12 weeks, Continuously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity will be evaluated according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 3 |  | Assessments approximately every 3 weeks throughout the duration of the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as determined by estimates of objective response rates and response duration |  | Efficacy measured every 6 weeks until week 48, then every 12 weeks | 
| PK for BMS-908662 as determined by minimum and maximum observed concentrations, time of maximum observed concentration, area under the concentration curve for one dosing interval and the accumulation index |  | PK measured during first 4 weeks on study | 
| PD will be assessed by evaluating markers of RAS/RAF pathway activity |  | PD assessed during the first 4 weeks on study |