Phase II study of vemurafenib in patients with locally advanced, unresectable stage IIIc or metastatic melanoma and activating exon 15 BRAF mutations other than V600E.

Abstract

9075^ Background: Approximately 50% of metastatic melanoma are activating BRAF mutation-positive, most commonly in codon V600. Vemurafenib (VEM), an inhibitor of oncogenic BRAF kinase, has been shown to improve progression-free survival (PFS) and overall survival (OS) in pts with advanced V600E-mutated melanoma (Chapman et al, 2011; NEJM). An open-label phase II trial (NCT01586195) is being conducted to determine the activity and safety of VEM in previously treated or untreated stage IIIC or IV melanoma pts with measurable disease and an activating, non-V600E BRAF mutation at exon 15 detected by centralized DNA sequencing. Methods: Eligible pts received oral VEM (960 mg bid) until disease progression, unmanageable toxicity, pt request for discontinuation, or other protocol-specified criteria. Tumor responses were evaluated per RECIST v1.1. The primary endpoint was investigator-assessed objective response rate. Time to response, duration of response, PFS and OS, 6- and 12-month survival rates, and safety w...