5-Year Update On Columbus: A Randomized Phase Iii Trial Of Encorafenib (Enco) Plus Binimetinib (Bini) Versus Enco Or Vemurafenib (Vem) In Patients (Pts) With Braf V600-Mutant Melanoma

Combined BRAF/MEK inhibitor therapy has demonstrated benefits on progression-free survival (PFS) and overall survival (OS) and is standard of care for the treatment (tx) of advanced BRAF V600-mutant (BRAFV600) melanoma. Here we report additional data from the 5-year update of the ongoing COLUMBUS trial. In COLUMBUS Part 1, 577 pts with advanced/metastatic BRAFV600 melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to enco 450 mg once daily + bini 45 mg twice daily, enco 300 mg once daily, or vem 960 mg twice daily. An updated analysis was conducted after 65 months’ minimum follow-up. Data are as is. In the enco + bini arm, the 5-year OS rate (95% CI) in all pts (n=192), those with lactate dehydrogenase (LDH) ≤ upper limit of normal (ULN) at baseline (n=137), and low tumor burden (n=88) was 35% (28–42), 45% (36–53), and 48% (37–58), respectively (data cut-off: Sep 15, 2020). Other efficacy results are shown in the table. Safety results were consistent with the known tolerability profile of enco + bini. Adverse events (AEs) occurring in ≥ 20% of enco + bini pts were nausea, diarrhea, vomiting, arthralgia, fatigue, increased blood creatinine phosphokinase (CPK), headaches, constipation, asthenia, and pyrexia. Grade 3/4 AEs occurring in ≥ 2.5% of pts in the enco + bini were hypertension, pyrexia, abdominal pain, diarrhea, and vomiting. Grade 3/4 abnormal laboratory values occurring in ≥ 2.5% pts in the enco + bini arm were increased gamma-glutamyl transferase, increased blood CPK, anemia, increased alanine transaminase, and hyperglycemia. 12%–14% of pts in each arm discontinued tx due to AEs. The most common anti-cancer tx after enco + bini were checkpoint inhibitors. Additional analyses will be presented.Table: 1041MOEnco + bini (n=192)Enco (n=194)Vem (n=191)5-year PFS rate*23 (16–30)19 (13–27)10 (5–18)5-year OS rate* LDH ≤ ULN n LDH > ULN n Low tumor burden n35 (28–42) 45 (36–53) 137 9 (3–18) 55 48 (37–58) 8835 (28–42) 42 (33–50) 147 14 (6–26) 47 50 (39–60) 9421 (16–28) 28 (21–36) 139 4 (1–12) 52 38 (28–49) 84Objective response rate*64 (57–71)52 (44–59)41 (34–48)Disease control rate*92 (87–96)84 (78–89)81 (75–86)Complete response†27 (14)15 (8)16 (8)Partial response†96 (50)85 (44)62 (32)Stable disease† (includes non-complete response or non-progressive disease)54 (28)63 (32)77 (40)Progressive disease† (includes best response of unknown or no assessment)15 (8)31 (16)36 (19)*% (95% CI) †n (%) Open table in a new tab *% (95% CI) †n (%) Updated results with enco + bini indicate continued long-term benefit in pts with advanced/metastatic BRAFV600 melanoma.