Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a median overall survival of < 1 year. A subset of PDAC is characterized by a homologous recombination deficiency (HRD). The most well-defined patients within this group are those with deleterious mutations in BRCA1, BRCA2 and PALB2. This subset of tumors respond exceptionally well to treatment with platinum agents, leading to durable responses. However, cumulative toxicity can complicate or even prevent continued therapy, and there is an unmet need to establish maintenance strategies for such patients.Prior studies have shown that BRCA1 and BRCA2 associated PDACs respond to PARP inhibitors. Cross-resistance to platinum and PARP inhibitors exists, so initiating PARP inhibitor therapy after the development of platinum-resistance is an inferior approach. In this setting, we have designed a phase II trial of rucaparib as maintenance therapy for patients with deleterious BRCA1, BRCA2 or PALB2 who have sustained stability on platinum-based treatment. Methods: We have enrolled 2 of 42 planned patients on study NCT03140670. Eligibility criteria include inoperable PDAC, a known somatic or germline deleterious mutation in BRCA1, BRCA2 or PALB2 and stability on platinum-based chemotherapy for ≥16 weeks. Patients who have progressed on platinum-based treatment or who have received prior therapy with PARP inhibitors are excluded. Patients will receive oral rucaparib twice daily continuously in 28-day cycles. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include response rate, duration of response and overall survival. A pre-treatment tumor biopsy and biopsy at progression will be obtained, as well as serial blood collections for circulating tumor material. Correlative assays will include tumor and circulating tumor DNA sequencing to identify genomic predictors of outcome and study resistance mechanisms. Clinical trial information: NCT03140670