The safety and tolerability of veliparib (V) plus capecitabine (C) and radiation (RT) in subjects with locally advanced rectal cancer (LARC): Results of a phase 1b study.

3634 Background: Patients (pts) with LARC treated with neoadjuvant RT/C and then surgery have significant relapse rates with low rates of complete response. V is a potent, orally bioavailable PARP inhibitor that has been shown to enhance the efficacy of chemotherapy and RT in preclinical models. This study sought to establish the recommended phase 2 dose (RPTD) as well as to assess safety, pharmacokinetics (PK), and preliminary activity of V + RT/C in pts with LARC. Methods: Pts with stage II-III rectal cancer received RT (50.4Gy/1.8Gy/fraction) with C (825 mg/m2BID) five days per week (W) for 5.5W. Dosing of V (BID, 20mg-400mg) continued from W1D2 to 2 days past RT. Pts underwent surgery 5-10W following RT. Assessments include identification of RPTD with the Exposure Adjusted Continual Reassessment Method, adverse events (AEs), PK, and pathological response: no disease present on pathologic review (ypCR), microscopic disease only (yCR), and tumor downstaging. Results: As of Dec 8, 2013, 18 pts have been ...