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

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.