Background: Pre-clinical studies report a critical role of c-KIT mutations in some mucosal, acral, solar, and vulvovaginal melanomas. Clinical trials of KIT-directed therapy with imatinib and sunitinib demonstrated activity in these subtypes. Unlike other TKIs, dasatinib has activity in melanoma cell lines with the most common KIT mutation at exon 11^L576P. E2607 assessed the efficacy of dasatinib in treatment-naïve or previously-treated patients (pts) with unresectable melanoma of these subtypes. Methods: Pts were assigned to receive dasatinib 70 mg PO twice daily with adjustment for toxicity. The primary objective for this two-stage phase II trial was response rate (RR: RECIST). Stage I was open to KIT mutated (KIT+) and wild-type (KIT-) tumors with mucosal, acral, and solar melanomas (n = 57). Depending upon the interim analysis, stage II would be for pts with KIT+ (n = 30) tumors; to enrich for KIT+, vulvovaginal was added and solar melanomas removed. Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety. Results: From May 2009 to Dec 2010, 57 pts were accrued to stage I. These data were presented at ASCO 2012. Three pts had KIT+ tumors, with 13.2+ months (mo) as the longest OS. Stage II opened in Nov 2011, accrued 24 pts with KIT+ tumors, and closed in Dec 2015 due to slow accrual. Six pts had mucosal (25%), 9 acral (37.5%), and 9 vulvovaginal melanomas (37.5%). As of Jan 2016, 16/24 have progressed (median PFS: 4.0 mo, 95% CI: 1.3-25.0) and 14/24 died (median OS: 12.3 mo, 4.5-29.7). Among 10 surviving pts, median follow-up is 15.2 mo (0.5-36.1 mo). Of 17 pts from stage II with mature response data, 4 had partial response (PR: 23.5%), 6 stable disease (35%), 5 progression (29.5%), and 2 were unevaluable (12%). Grade III (11/23: 48%) treatment-related toxicities were fatigue, (5 pts), anemia (3 pts) and dyspnea (2 pts). One pt had grade IV dyspnea. Conclusions: E2607 is closed to accrual, and finalized results, including type of KIT mutation and durations of disease control from stages I and II will be presented. Among pts with these KIT+ melanoma subtypes, dasatinib is an active agent. Clinical trial information: NCT00700882