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

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: BMS-908662; Drug: BMS-908662; Drug: Ipilimumab; Drug: Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • New York
    • New York, New York, United States, 10065
      • Jedd D. Wolchok, Md,Phd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMS-908662 or Ipilimumab (A)	Drug: BMS-908662; Capsules, Oral, escalating doses starting at 25 mg, Q 12 h daily, Continuously; Drug: BMS-908662; 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; Drug: Ipilimumab; Vial, IV, escalating doses starting at 3 mg/kg, Once every 3 weeks for 6 weeks, then once every 12 weeks, Continuously; Drug: Ipilimumab; Vial, IV, escalating doses starting at 3 mg/kg, Once every 6 weeks for 4 cycles, then once every 12 weeks, Continuously
Experimental: BMS-908662 or Ipilimumab (B)	Drug: BMS-908662; Capsules, Oral, escalating doses starting at 25 mg, Q 12 h daily, Continuously; Drug: BMS-908662; 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; Drug: Ipilimumab; Vial, IV, escalating doses starting at 3 mg/kg, Once every 3 weeks for 6 weeks, then once every 12 weeks, Continuously; Drug: Ipilimumab; Vial, IV, escalating doses starting at 3 mg/kg, Once every 6 weeks for 4 cycles, then once every 12 weeks, Continuously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: November 19, 2010
• First Submitted That Met QC Criteria: November 19, 2010
• First Posted (Estimate): November 22, 2010

Study Record Updates

• Last Update Posted (Estimate): June 12, 2013
• Last Update Submitted That Met QC Criteria: June 11, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: CA206-005