Veliparib (Abt-888) Extended-Release Formulations: A Phase 1 Study On Safety, Pharmacokinetics (Pk), And Bioavailability In Patients With Advanced Solid Tumors.

2579Background: Veliparib is a potent oral PARP1/2 inhibitor. Monotherapy trials with immediate release formulation veliparib (IR-v) showed antitumor activity in BRCA+ cancers. An extended release formulation (ER-v) may lower the peak-to-trough concentration ratio while maintaining exposure and improving tolerability, providing a rationale to conduct a phase 1 study (NCT01853306) of ER-v in pts with advanced tumors. Methods: Eligible pts had metastatic BRCA+ cancer, BRCA± high-grade serous ovarian/primary peritoneal/fallopian tube cancer (OC), (part 1/2), or BRCA+ breast cancer (BC), or OC (part 3). Part 1 – PK assessment: pts received ER-v (3 different ER-vs tested) or IR-v 200 mg in fed/fasted state on days 1/3/5 (3-group, single-sequence crossover). Part 2 – 3+3 dose escalation: pts received ER-v daily (QD or BID) starting at 200 mg. Part 3 – safety expansion: ER-v was administered continuously at the RP2D. Primary objectives were to determine the bioavailability and food effect of ER-v vs IR-v, the MT...