A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours.

ABSTRACT: BACKGROUND:Veliparib is a potent poly(ADP-ribose) polymerase inhibitor. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of veliparib combined with various FOLFIRI regimens in patients with solid tumours. METHODS:Patients received veliparib (10-270?mg BID, days 1-5, 15-19) and FOLFIRI (days 1-3, 15-17) in three regimens containing 5-fluorouracil 2,400?mg/m2: irinotecan 150?mg/m2 and folinic acid 400?mg/m2 (part 1); irinotecan 180?mg/m2, folinic acid 400?mg/m2, and 5-fluorouracil 400?mg/m2 bolus (part 2), or irinotecan 180?mg/m2 (part 3). The RP2D was further evaluated in safety expansion cohorts. Preliminary antitumour activity was also assessed. RESULTS:Ninety-two patients received ?1 veliparib dose. MTD was not reached; RP2D was set at 200?mg BID veliparib plus FOLFIRI (without 5-fluorouracil bolus). Most common treatment-emergent adverse events were neutropenia (66.3%), diarrhoea, and nausea (60.9% each). Dose-limiting toxicities (n?=?4) were grade 3 gastritis and grade 4 neutropenia and febrile neutropenia. Veliparib exposure was dose-proportional, with no effects on the pharmacokinetics of FOLFIRI components. Fifteen patients had a partial response (objective response rate, 17.6%). CONCLUSIONS:The acceptable safety profile and preliminary antitumour activity of veliparib plus FOLFIRI support further evaluation of this combination.

SUBMITTER: Berlin J 

PROVIDER: S-EPMC5933261 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature