A Study to Evaluate the Safety 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.
Cobimetinib: Once daily (QD) or three times weekly (TIW) for 21 days, 7 days off
Nivolumab: Once every 4 weeks (Q4W)
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* ECOG Performance Status of 0 or 1
* Histologically confirmed, metastatic (recurrent or de novo Stage IV) or unresectable locally advanced (Stage III) cutaneous melanoma, that has progressed on or after treatment with anti-PD-1 or anti-PD-L1 therapy. Patients may have received up to two lines of systemic cancer therapy. Treatment with anti-PD-1/PD-L1 in the adjuvant setting is acceptable. Patients must have progressed disease at study entry
* Documentation of NRAS mutation-positive within 5 years prior to screening
* Tumor specimen availability
* Adequate hematologic and end-organ function
* Measurable disease per RECIST v1.1
Exclusion Criteria:
* Prior treatment with a pan-RAF inhibitor
* Treatment with systemic immunotherapy agents (e.g., anti-CTLA4, anti-PD(L)1, cytokine therapy, investigational therapy, etc.) within 28 days prior to C1D1
* Symptomatic, untreated, or actively progressing CNS metastases
* History or signs/symptoms of clinically significant cardiovascular disease
* Known clinically significant liver disease
* History of autoimmune disease or immune deficiency
* Prior treatment with a MEK inhibitor (cobimetinib arm)
* History of or evidence of retinal pathology on ophthalmologic examination (cobimetinib arm)
* History of immune-related AE attributed to prior anti-PD(L)1 therapy that resulted in permanent discontinuation of anti-PD(L)1 therapy (nivolumab arm)
Primary outcome measure(s)
Percentage of Participants With Dose Limiting Toxicity (DLTs) — 28 Days from Cycle 1, Day 1
Percentage of Participants With Adverse Events — From Cycle 1, Day 1 Up to 4 Years Severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0
Trial sites (18)
Facility
City
Region
Status
California Pacific Medical Center Research Institute
San Francisco
California
UCSF Helen Diller Family CCC
San Francisco
California
University of Colorado Cancer Center
Aurora
Colorado
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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