Safety and Efficacy in Participants With Metastatic BRAF-mutant Melanoma Treated With Encorafenib With and Without Binimetinib in Combination With Nivolumab and Low-dose Ipilimuma

Study Summary

Patients with unresectable or metastatic BRAF-mutant melanoma high-risk patients will be given 450 mg orally (PO) daily (QD) plus binimetinib 45 mg PO twice daily (BID) together with nivolumab administered intravenously (IV) at 3mg/kg and ipilimumab administered IV at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab administered IV at 480mg every 4 weeks until progression or discontinuation due to toxicity. Concurrently, a triple therapy arm will be explored with encorafenib 300 mg PO QD together with ipilimumab administered IV at 1mg/kg and nivolumab 3mg/kg IV every 3 weeks for 4 doses, followed by nivolumab administered at 480mg every 4 weeks until progression or discontinuation due to toxicity. Tolerability of the two arms will be compared, and a recommended phase 2 dose (RP2D) will be determined. After determination of treatment schedule, expansion cohorts will further explore the preliminary efficacy and further describe the toxicity profile of the triplet or quadruplet regimen in high-risk cohorts including symptomatic brain metastases or liver metastases with elevated lactate dehydrogenase (LDH) or bulky systemic disease burden.

Primary Outcome

Determination of recommended phase II dose (RP2D) of triple therapy in patients treated with 300mg encorafenib, 3mg/kg nivolumab and 1mg/kg ipilimumab via the frequency of DLTs that are classified as either possibly, probably, or definitely related to study treatment according to NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0). Number of distinct patients experiencing Adverse events and DLTs. This will be done with continuous Bayesian toxicity monitoring.

Interventions

• DRUG binimetinib
• DRUG nivolumab
• DRUG ipilimumab
• DRUG encorafenib