A phase I study of veliparib (ABT-888) in combination with weekly carboplatin and paclitaxel in advanced solid malignancies and enriched for triple-negative breast cancer (TNBC).

1015 Background: Veliparib (ABT-888) is an oral, potent small molecule inhibitor of poly-ADP-ribose polymerase (PARP). The combination of veliparib (V) with carboplatin (C) and paclitaxel (P) dosed every 3 weeks has been shown to be safe with early signs of efficacy in a phase I study conducted by our group. In breast cancer patients (pts), weekly P improves disease-free and overall survival vs. every three week P with comparable safety (ECOG 1199), thus supporting the exploration of weekly C and P in combination with V. This study is designed to determine the recommended phase 2 dose (RP2D), maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), adverse events (AEs), anti-tumor activity, and pharmacokinetic (PK) parameters of this combination. Methods: A standard 3+3 design was used with 4 escalating V dose levels ranging from 50-200 mg bid. C (AUC 2) and P (80 mg/m2) were administered on a weekly basis over a 21-day cycle on all dose levels. Dose escalation was followed by dose expansion in pts ...