1113P COLUMBUS 7-year update: A randomized, open-label, phase III trial of encorafenib (enco) + binimetinib (bini) vs vemurafenib (vemu) or enco in patients (pts) with BRAF V600–mutant melanoma

In the randomized, 2-part, multicenter, open-label, phase III COLUMBUS study, enco + bini (approved in the US, EU, and other countries) and enco alone improved PFS and OS rates vs vemu in patients with BRAF V600–mutant metastatic melanoma. Here we report data from the 7-year analysis of COLUMBUS part 1. Pts with advanced or metastatic BRAF V600–mutant melanoma were randomized 1:1:1 to enco 450 mg QD + bini 45 mg BID, vemu 960 mg BID, or enco 300 mg QD. Pts were treatment (tx)-naive or had progression after 1L immunotherapy. No prior BRAF/MEKi was allowed. Randomization was stratified by cancer stage (IIIB + IIIC + IVM1a + IVM1b vs IVM1c), ECOG PS (0 vs 1), and prior 1L immunotherapy (yes vs no). 577 pts were randomized to enco + bini (n=192), vemu (n=191), or enco alone (n=194). Updated analyses were conducted after >93 mo of minimum follow-up (cutoff: Jan 13, 2023). The 7-year PFS and OS rates (95% CI) were 21.2% (14.7, 28.4) and 27.4% (21.2, 33.9) in the enco + bini arm and 6.4% (2.1, 14.0) and 18.2% (12.8, 24.3) in the vemu arm, respectively. TEAEs (≥30% with enco + bini) were nausea, diarrhea, vomiting, arthralgia, and fatigue. Grade 3/4 TEAEs (≥5% with enco + bini) were γ-glutamyltransferase increased, blood CPK increased, hypertension, ALT increased, and anemia. Across arms, 16% to 20% of pts discontinued tx due to AEs. After tx discontinuation, 15% of pts from the enco + bini arm, 42% from the vemu arm, and 28% from the enco alone arm received BRAF/MEKi tx; 42% from the enco + bini arm, 49% from the vemu arm, and 43% from the enco alone arm received checkpoint inhibitors. With a median duration of follow-up of 100 mo, the 7-year analysis from COLUMBUS part 1 confirms the long-term, sustained efficacy and known safety profile of enco + bini, with no new safety signals emerging, in pts with BRAF V600–mutant metastatic melanoma.Table: 1113PBy BICREnco + bini (n=192)Vemu (n=191)Enco alone (n=194)mPFS, mo (95% CI)14.9 (11.0, 20.2)7.3 (5.6, 7.9)9.6 (7.4, 14.8)mOS, mo (95% CI)33.6 (24.4, 39.2)16.9 (14.0, 24.5)23.5 (19.6, 33.6)7-year PFS rate, % (95% CI)21.2 (14.7, 28.4)6.4 (2.1, 14.0)15.8 (9.3, 23.8)7-year OS rate, % (95% CI)27.4 (21.2, 33.9)18.2 (12.8, 24.3)31.7 (24.9, 38.7)Best overall response, n (%)CR29 (15.1)16 (8.4)17 (8.8)PR94 (49.0)62 (32.5)83 (42.8)SDa54 (28.1)77 (40.3)63 (32.5)PDb15 (7.8)36 (18.9)31 (16.0)ORR, % (95% CI)64.1 (56.8, 70.8)40.8 (33.8, 48.2)51.5 (44.3, 58.8)DCR, % (95% CI)92.2 (87.4, 95.6)81.2 (74.9, 86.4)84.0 (78.1, 88.9)aIncludes non-CR/non-PD. bIncludes best response of unknown or no assessment. Open table in a new tab