Pimasertib plus gemcitabine in metastatic pancreatic adenocarcinoma: Results of a safety run-in part of a phase II trial.

4041 Background: Activating MAPK pathway mutations (predominantly RAS) occur with a high incidence in metastatic pancreatic adenocarcinoma (mPaCa). Pimasertib is a MEK1/2 inhibitor with potent activity in cell lines and xenografts with an activated MAPK pathway. This two-part trial in patients (pts) with mPaCa comprises a dose-escalation safety run-in and a randomized phase II part (EudraCT 2009-011992-61). We defined the maximum tolerated dose (MTD), safety, pharmacokinetics (PK) and antitumor activity of two pimasertib dosing schedules (S), and the recommended phase II dose (RP2D). Methods: Dose-escalation (3+3 design) in two dosing S of oral pimasertib: once-daily (qd) - 5 days on, 2 days off (S1); and twice-daily (bid) - continuous (S2) combined with the standard dose of gemcitabine (gem). Results: 53 pts (median age 61 years and ECOG performance status 0-1) have been treated at six dose levels in S1 (15 to 120 mg qd) and at 60 and 75 mg bid in S2. MTDs were defined as 120 mg qd and 75 mg bid. Two pts...