Updated efficacy and safety results from the phase I study of intermittent dosing of the dual MEK/RAF inhibitor, RO5126766 in patients (pts) with RAS/RAF mutated advanced solid tumours.

2582Background: RO5126766 is a novel MEK inhibitor with functional RAF inhibition. A dose escalation Phase 1 study, comparing 2 intermittent schedules, has previously been reported, with a recommended phase 2 dose (RP2D) of 4 mg twice weekly (Monday/Thursday (M/Th)). We now present results from the expansion cohort of this study, which aims to assess tolerability and preliminary activity in pts with KRAS, NRAS or BRAFmutated tumours. Methods: Pts with KRAS, NRAS or BRAF mutated tumours were treated with RO5126766 at the RP2D dose of 4 mg M/Th in 4 week cycles. Tumour assessment was performed with CT imaging every 2 cycles. Tumour pharmacodynamics was assessed in pre and post treatment biopsies where available. Results: To date, 18 evaluable pts (8 Non Small Cell Lung Carcinoma (NSCLC), 4 colorectal, 3 ovarian, 1 endometrial, 1 uterine carcinosarcoma, 1 melanoma) have been treated. Pts had received 1-7 (median 3) lines of treatment previously. Skin rashes were common G1-2 12pts, G3-4 4pts. Other adverse ev...