This study will evaluate the safety, pharmacokinetics, and activity of belvarafenib as a single agent and in combination with either cobimetinib or cobimetinib plus nivolumab in patients with NRAS-mutant advanced melanoma who have received anti-PD-1/PD-L1 therapy.
The study will evaluate three treatment regimens in three arms: a belvarafenib monotherapy arm (Belva arm); a belvarafenib plus cobimetinib arm (Belva + Cobi arm) in an initial dose-finding phase followed by an expansion phase and a belvarafenib plus cobimetinib plus nivolumab arm (Belva + Cobi + Nivo arm) in a run-in phase followed by an expansion phase.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
65
Twice daily (BID), continuous dosing
Once daily (QD) or three times weekly (TIW) for 21 days, 7 days off
Once every 4 weeks (Q4W)
California Pacific Medical Center Research Institute
San Francisco, California, United States
UCSF Helen Diller Family CCC
San Francisco, California, United States
Percentage of Participants With Dose Limiting Toxicity (DLTs)
Time frame: 28 Days from Cycle 1, Day 1
Percentage of Participants With Adverse Events
Severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0
Time frame: From Cycle 1, Day 1 Up to 4 Years
Objective response rate (ORR) according to RECIST v1.1
Defined as the percentage of participants with a CR or PR on two consecutive occasions \>/= 4 weeks apart, as determined by the investigator according to RECIST v1.1
Time frame: Up to Approximately 4 Years
Progression free survival (PFS) according to RECIST v1.1
Defined as the time from the first study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Time frame: Up to Approximately 4 Years
Duration of response (DOR) according to RECIST v1.1
Defined as the time from the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Time frame: Up to Approximately 4 Years
Overall survival (OS)
Defined as the time from the first study treatment to death from any cause
Time frame: Up to Approximately 4 Years
Plasma concentration of belvarafenib at specified timepoints
Time frame: Up to 30 Days After the Final Dose of Study Drug
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University of Colorado Cancer Center
Aurora, Colorado, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Washington University School of Medicine
St Louis, Missouri, United States
Memorial Sloan Kettering
New York, New York, United States
Calvary Mater Newcastle
Waratah, New South Wales, Australia
Peter MacCallum Cancer Centre-East Melbourne
Melbourne, Victoria, Australia
Linear Clinical Research Ltd
Nedlands, Western Australia, Australia
Ottawa Hospital Regional Cancer Centre
Ottawa, Ontario, Canada
...and 7 more locations
Plasma concentration of cobimetinib at specified timepoints
Time frame: Up to 30 Days After the Final Dose of Study Drug