ABSTRACT Aim: Few treatment options exist for pts with BRAF-mutant mCRC. Encorafenib, a potent and selective oral BRAF inhibitor, showed signs of efficacy in pts with BRAF-mutant advanced melanoma in a phase 1 dose-escalation study. Here we present results from pts with BRAF-mutant mCRC enrolled in the dose-expansion phase of the same trial. Methods: Adult pts with nonresectable, advanced mCRC with a BRAF V600 mutation, for whom there was no existing effective therapy, received encorafenib 300 mg (n = 6) or 450 mg (n = 12) once daily. Responses were assessed by investigator per RECIST 1.1. Results: All 18 pts had a BRAF V600E mutation. Median age was 62 y (range, 34-73). Ten pts (55.6%) were female. Median number of prior treatment regimens was 3 (range, 1-8); 1 pt received prior therapy with a BRAF inhibitor (vemurafenib). At the data cutoff (7 Jan 2014), median treatment duration was 11 wks; 4 pts (22.2%) remained on treatment, and 14 (77.8%) discontinued due to progressive disease (PD; n = 10), adverse events (AEs; n = 3), and death (n = 1, not related to study drug). Twelve pts (66.7%) achieved a best response of stable disease (SD). No pt achieved confirmed complete response (CR) or confirmed partial response (PR) by the data cutoff (Table). Progression-free survival (PFS) events occurred in 13 pts (PD, n = 10; death, n = 3). Median PFS was 4.0 mo. The most common AEs of any grade were palmar-plantar erythrodysaesthesia syndrome (66.7%), myalgia (44.4%), and dry skin (44.4%). Three pts had dose-limiting toxicities (arthralgia and myalgia [n = 1]; insomnia and myalgia [n = 1]; bone pain and vomiting [n = 1]; all grade 3), all on encorafenib 450 mg. Encorafenib 300 mg n = 6 Encorafenib 450 mg n = 12 All pts N = 18 Best Overall Response, n (%) _CRa 0 0 0 _PRa 0 0 0 _SD 4 (66.7) 8 (66.7) 12 (66.7) __With unconfirmed CR/PR 1 (16.7) 2 (16.7) 3 (16.7) _PD 1 (16.7) 3 (25.0) 4 (22.2) __With unconfirmed CR/PR 0 2 (16.7) 2 (11.1) _Unknownb 1 (16.7) 1 (8.3) 2 (11.1) Median PFS, mo (95% CI) 2.3 (1.7-7.2) 4.0 (1.8-5.5) 4.0 (1.8-5.6) a CR and PR required confirmation in a second assessment at least 4 wks after the first. b Best response was unknown for 2 pts who achieved SD before 6 wks of treatment. Conclusions: Encorafenib showed modest activity in this difficult-to-treat population, with SD observed in two-thirds of pts. Studies in BRAF-mutant mCRC are ongoing in combination with epidermal growth factor receptor and phosphoinositide 3-kinase inhibitors. Disclosure: M. Hidalgo: has been on a board of directors and/or advisory board for and received research funding from Novartis; R. von Moos: has consulted for Novartis, Roche, GSK, BMS, MSD; received research funding from Amgen, Merck, Roche; received honoraria from Novartis, Roche, GSK, BMS, Sanofi; A. Arance: has received research funding from Roche; has consulted with Roche, BMS, GSK D. Michel, A. Seroutou and T. Demuth: is an employee of Novartis Pharma AG; J. Tabernero: has consulted for Amgen, Imclone, Lilly, Merck KGaA, Millenium, Novartis, Roche, Sanofi, Celgene, Chugai, Taiho and has received honoraria from Amgen, Merck KGaA, Novartis, Roche, Sanofi. All other authors have declared no conflicts of interest.