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.

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)