Phase I study of combination vemurafenib, carboplatin, and paclitaxel in patients (pts) with BRAF-mutant advanced cancer.

105 Background: Although BRAF inhibitors have demonstrated efficacy, resistance develops in most pts. We hypothesized that BRAF inhibitor vemurafenib, in combination with carboplatin and paclitaxel, would be well-tolerated and overcome resistance. Methods: We designed a phase I study (3+3 design) to determine safety of vemurafenib (480-960 mg twice a day) with carboplatin (AUC 5-6 q3 weeks) and paclitaxel (75-175 mg/m2 q3 weeks). Endpoints included maximum tolerated dose (MTD), dose limiting toxicity (DLT), and response (RECIST 1.1). Results: To date, 19 pts have enrolled. Pts received vemurafenib (480-720 mg twice a day), carboplatin (AUC 5-6) q3 wks, and paclitaxel (100-135 mg/m2) q3 wks. Median age was 53 yrs (range 33-75) with median of 4 prior systemic therapies (range 1-7). Eleven pts (58%) had received prior BRAF inhibitors, 3 pts (16%) MEK inhibitors, 8 pts (42%) platinum therapy, and 3 pts (16%) taxane therapy. Pts (13/19 [68.4%] with melanoma and n = 1 pt each of cholangiocarcinoma, histiocytoma...