Background: PC is characterized by DNA Damage Repair (DDR) deficiencies, including in BRCA1/2, ATM, and FANC genes. Given preclinical synergism between veliparib with irinotecan, safety and preliminary efficacy, we designed a randomized phase II study of mFOLFIRI (no 5-FU bolus) + veliparib vs FOLFIRI alone for 2nd line mPC patients (pts). Methods: Eligible pts had mPC, adequate organ function, ECOG PS 0-1, and 1 prior non-irinotecan systemic therapy.143 pts were to be randomized (1:1) to veliparib vs control. Primary endpoint was overall survival (OS). All pts had blood and tumor biopsies at baseline to assess germline and somatic BRCA1/2 mutations (integrated), and homologous recombination (HR) or DDR biomarkers (exploratory). Results: 123 pts were accrued between 09/2016 to 12/2017, and 108 were included in this analysis. 117 pts were biomarker evaluable: 109 blood/106 tumors. 11 cancers (9%) had HR deficiency (HRD), including 4 germline (BRCA1, BRCA2, ATM) and 7 somatic mutations (BRCA2, PALB2, ATM, CDK12). Additional 24 cancers (20%) had germline (n = 11, e.g., FANC, BLM, SLX4, CHEK2) or somatic mutations (n = 13, e.g., FANC, BLM, POLD1, RIF1, MSH2, MSH6) in other DNA repair genes, not classified as HRD. A planned interim futility analysis at 35% of expected PFS events determined the veliparib arm was unlikely to be superior to control. Most common grade 3/4 treatment related toxicities were neutropenia (33% vs 20%), fatigue (19% vs 4%), and nausea (11% vs 4%), for veliparib vs control. Treatment exposure was similar for veliparib vs control: median 4 cycles (range 1-31 vs 1-32). Median OS was 5.1 vs 5.9 mos (HR 1.3, 95%CI 0.9-2.0, p = 0.21), and median PFS was 2.1 vs 2.9 mos (HR 1.5, 95%CI 1.0-2.2, p = 0.05) for veliparib vs control arms, respectively. Correlations of gene mutations and signatures with efficacy outcomes will be presented. Conclusions: Nearly 30% of mPC pts had DNA repair gene abnormalities, including 9% with HRD. Veliparib increased toxicity and did not improve OS when added to mFOLFIRI in biomarker unselected pts. BRCA1/2 and DDR biomarkers will be correlated with efficacy to inform patient selection for future PARP inhibitor clinical trials. Clinical trial information: NCT02890355