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4131 Background: We recently reported the results of a single arm phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic variant in BRCA1, BRCA2, or PALB2 (NCT 03140670; Reiss, JCO 2021). However, optimal treatment following progression on PARP inhibitors (PARPi) has not been defined. Here, we report a descriptive study of post-progression treatment and outcomes of this patient population. Methods: Patients with advanced pancreatic cancer and germline or somatic BRCA1, BRCA2, or PALB2mutations treated with at least 16 weeks of platinum-based chemotherapy without progression were enrolled and treated with rucaparib until progression or unacceptable toxicity. At the time of progression, patients were treated with physician-choice chemotherapy. Here we evaluate the objective response rates (ORR) by RECIST 1.1. Overall survival (OS) and time to second progression (PFS2) calculated from trial enrollment and progression free survival on chemotherapy (PFS) by regimen were secondary endpoints. Time-to-event was analyzed by the Kaplan-Meier method and censored at date of last clinic visit, with a cutoff date of 12/10/21. Results: The trial enrolled 42 patients; 31 patients had progressed. Of these, 22 received second-line chemotherapy: nine were treated with an oxaliplatin-based regimen, nine were treated with a cisplatin-based regimen, and four were treated with non-platinum regimens. Demographics were balanced between those who received platinum versus non-platinum. All patients who received second-line chemotherapy regimens met the PFS2 endpoint and all but one patient had died at time of data cutoff. No patients had a complete response, five patients had a partial response (PR). By regimen, 1/9 patients treated with cisplatin had a PR, 3/9 treated with oxaliplatin had a PR, and 1/4 patients treated with non-platinum had a PR. OS, PFS2, PFS, and ORR results by regimen are shown in the table. Conclusions: In this small sample of patients with advanced pancreatic cancer with progressive disease on PARPi, chemotherapy retains some activity. Further study to identify predictors of response and/or resistance to post-PARPi treatment are underway. [Table: see text]