Overview
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.
Principal investigator
Eligibility criteria
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)
* 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)
For Referring Providers
Do you have a patient you think would be a good candidate for this trial? Learn more about enrolling your patient.