Phase I Trial Of First-In-Class Atr Inhibitor Vx-970 In Combination With Gemcitabine (Gem) In Advanced Solid Tumors (Nct02157792).

2513Background: ATR is a regulator of the cellular response to replication stress, where it signals DNA damage repair through the homologous recombination pathway.Many cancer cells depend on ATR to survive DNA damage. VX-970 is a potent, selective inhibitor of ATR with marked preclinical anticancer activity in combination with DNA-damaging chemotherapy in preclinical models. A multicenter phase I study of VX-970 in combination with Gem was performed. Methods: Patients (pts) with advanced solid tumors measurable by RECIST 1.1 received IV VX-970 in combination with Gem in a 3+3 dose-escalation design. Gem was administered on days 1 and 8 and VX-970 on days 2, 9 and 16 of each 21-day cycle. Results: 50 pts were treated (28 M/22 F), median age 62 yrs (range 28-79 yrs), ECOG PS 0/1: 15/35. Primary tumors were colorectal (n=15), NSCLC (n=6), breast (n=4), pancreatic (n=2) and other (n=23). Gr 3/4 treatment-related AEs occurred in 25 pts. Maximum tolerated dose was not reached. VX-970 exposure was approximately ...