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/m2, 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. The recommended phase 2 dose of veliparib, combined with fixed‐dose cisplatin and gemcitabine, is 80 mg by mouth twice daily on days 1 to 12 of a 3‐week cycle. Substantial antitumor activity has been identified in a germline BRCA‐mutated patient population with untreated advanced pancreatic adenocarcinoma.