VE-BASKET, a Simon 2-stage adaptive design, phase II, histology-independent study in nonmelanoma solid tumors harboring BRAF V600 mutations (V600m): Activity of vemurafenib (VEM) with or without cetuximab (CTX) in colorectal cancer (CRC).

3518^ Background: Low prevalence of V600m in non-melanoma cancers requires novel trial designs to assess the activity of BRAF inhibitors. Based on preclinical models that V600m positive (+) CRC upregulates the EGFR pathway and sensitizes to EGFR inhibitors in response to VEM (Prahallad et al Nature 2012), we investigated the activity of VEM in V600m+ CRC with or without CTX. Here we present preliminary efficacy and safety data for the VEM cohort and VEM + CTX dose-finding cohorts. Methods: This multicohort, Simon 2-stage adaptive design, single-proportion study included adult patients (pts) with V600m+ cancers refractory to standard therapy or for whom standard/curative therapy is not available. Pretreated CRC pts received either VEM (960 mg bid) without (cohort 3a) or with CTX (cohort 3b, 3+3 dose escalation) until investigator (INV)-assessed disease progression or unacceptable toxicity. Primary objective was INV-assessed response rate at wk 8 (RECIST v1.1). Maximum tolerated dose (MTD) and recommended d...