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Background: A phase 1 trial was used to evaluate a combination of cisplatin, gemcitabine, and escalating doses of veliparib in patients with untreated advanced pancreatic ductal adenocarcinoma (PDAC) in 2 cohorts: a germline BRCA1/2-mutated (BRCA+) cohort and a wild-type BRCA (BRCA-) cohort. The aims were to determine the safety, dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase 2 dose (RP2D) of veliparib combined with cisplatin and gemcitabine and to assess the antitumor efficacy (Response Evaluation Criteria in Solid Tumors, version 1.1) and overall survival., Methods: Gemcitabine and cisplatin were dosed at 600 and 25 mg/m 2 , respectively, over 30 minutes on days 3 and 10 of a 21-day cycle. Four dose levels of veliparib were evaluated: 20 (dose level 0), 40 (dose level 1), and 80 mg (dose level 2) given orally twice daily on days 1 to 12 and 80 mg given twice daily on days 1 to 21 (dose level 2A [DL2A])., Results: Seventeen patients were enrolled: 9 BRCA+ patients, 7 BRCA- patients, and 1 patient with an unknown status. DLTs were reached at DL2A (80 mg twice daily on days 1 to 21). Two of the 5 patients in this cohort (40%) experienced grade 4 neutropenia and thrombocytopenia. Two grade 5 events occurred on protocol. The objective response rate in the BRCA+ cohort was 7 of 9 (77.8%). The median overall survival for BRCA+ patients was 23.3 months (95% confidence interval [CI], 3.8-30.2 months). The median overall survival for BRCA- patients was 11 months (95% CI, 1.5-12.1 months)., Conclusions: The RP2D of veliparib was 80 mg by mouth twice daily on days 1 to 12 in combination with cisplatin and gemcitabine; the DLT was myelosuppression. Substantial antitumor activity was seen in BRCA+ PDAC. A randomized phase 2 trial is currently evaluating cisplatin and gemcitabine with and without veliparib for BRCA+ PDAC (NCT01585805). Cancer 2018;124:1374-82. © 2018 American Cancer Society., (© 2018 American Cancer Society.)