Encorafenib (enco) + binimetinib (bini) + pembrolizumab (pembro) for unresectable locally advanced or metastatic BRAF V600-mutant melanoma: Results from STARBOARD safety lead-in (SLI).

Abstract

9531 Background: BRAF inhibitors (BRAFi) + MEK inhibitors (MEKi) (eg, enco + bini) and immune checkpoint inhibitors (CPIs) (eg, pembro) are approved for patients (pts) with BRAF V600-mutant metastatic melanoma. Combinations of BRAFi + MEKi with CPIs further improve outcomes and may offer additional treatment strategies. STARBOARD (NCT04657991) is an ongoing randomized, double-blinded, placebo-controlled, phase 3 study of enco + bini + pembro vs pembro in pts with unresectable locally advanced or metastatic BRAF V600-mutant cutaneous melanoma. Here we present the SLI results. Methods: Key inclusion criteria were histologically confirmed unresectable/metastatic BRAF V600E/K-mutant cutaneous melanoma and ≤1 prior systemic therapy for unresectable/metastatic disease. Pts received enco 450 mg QD + bini 45 mg BID + pembro 200 mg IV Q3W (COMBO450+P) or enco 300 mg QD + bini 45 mg BID + pembro 200 mg IV Q3W (COMBO300+P). The primary objective was to identify the recommended phase 3 dose (RP3D). The primary endpoint was dose-limiting toxicity (DLT) incidence; secondary endpoints included safety, objective response rate (ORR), time to response (TTR), and PFS (post hoc). Results: 20 pts received COMBO450+P and 17 COMBO300+P (cutoff: Dec 2, 2022). See table for baseline characteristics. 1 pt had a DLT with COMBO450+P: Grade (G) 3 drug-induced liver injury with concurrent G4 ALT increase and G3 bilirubin increase that resolved. 2 pts had DLTs with COMBO300+P: 1 with G3 rheumatoid arthritis flare and 1 with inability to receive drug due to G4 arthralgia, G4 back pain, G4 pyrexia, G3 chills, G3 headache, G3 paranesthesia, and G3 maculopapular rash. Drug-related AEs led to permanent discontinuation in 4, 5, and 6 pts for enco, bini, and pembro, respectively. 1 pt in the COMBO300+P arm died <28 days after discontinuing all study treatments due to disease progression. See table for antitumor activity data. Conclusions: Safety across cohorts was comparable and consistent with the known safety profile of each agent. Both regimens were generally tolerable; COMBO450+P was chosen as the RP3D based on the totality of the safety data. The phase 3 portion of STARBOARD is ongoing. Clinical trial information: NCT04657991 . [Table: see text]