MLN2480, an investigational oral pan-RAF kinase inhibitor, in patients (pts) with relapsed or refractory solid tumors: Phase I study.

2547 Background: MLN2480 is an investigational pan-RAF kinase inhibitor. In vivo, MLN2480 showed antitumor activity in melanoma, colon, lung, and pancreatic cancer xenograft models. This first-in-human study aimed to evaluate the safety of MLN2480, determine the MTD/recommended phase 2 dose (RP2D), and evaluate pharmacokinetics (PK) and preliminary efficacy. Methods: Pts aged ≥18 yrs with advanced solid tumors who had failed/were not candidates for standard therapy received oral MLN2480 every other day (Q2D) in 22-d cycles, with dose escalation (3+3 design) based on DLTs in cycle 1. AEs were graded per NCI-CTCAE v4.03. Blood samples for plasma PK assessment were taken pre-dose and at multiple times post-dose, d 1 and 21, cycle 1. Results: 24 pts (10 male, median age 64.5 yrs [range 37–83]) have been treated at 20, 40, 80, 135, 200, and 280 mg (n=4, 3, 3, 3, 4, and 7), respectively. The most common tumors included colorectal cancer in 11 pts and non-small-cell lung cancer in 2 pts. Pts received a median of...