Background: Veliparib (V) is a potent, orally bioavailable PARP inhibitor that crosses the blood brain barrier. Phase 2 trials in BRCA pts as monotherapy or in unselected pts in combination with platinum-based chemotherapy have demonstrated evidence of efficacy. V plus radiation has shown promising efficacy in preclinical models and clinically in combination with WBRT. Methods: Pts were randomized 1:1:1 to WBRT plus V 50 mg BID (V50), V 200 mg BID (V200), or P BID. Treatment began within 28 days (d) of diagnosis. Pts received 30 Gray WBRT in 10 fractions. V50, V200, or P BID was self-administered starting on d 1 of WBRT and continuing until 1 d after completion. The primary endpoint was overall survival (OS). Survival was assessed at 2 month (m) intervals for 6 m then every 3 m (≥36 m). Pts who received ≥1 dose were included in the safety analyses; AEs were compared across arms using Fisher’s exact test. Results: 307 pts were randomized. OS, intracranial response rate, and time to clinical or radiographic progression were not statistically significantly different between any of the V arms and the P arm. There were no differences in all grade adverse drug reactions (ADRs) across arms and a modest improvement in grade 3/4 AEs in the V arms. Conclusions: Although preclinical and early clinical data suggested that V might synergize with radiotherapy, there was no difference in multiple study endpoints between V50 or V200 and P in this setting. Safety parameters observed in the V arms were generally similar to the P arm; no new safety signals of V were identified. Clinical trial information: NCT01657799

^a1 not dosed or included in the safety analysis; NR, not reached.