724 Background: Metastatic pancreatic cancer (mPC) with DNA damage repair (DDR) gene alterations, such as BRCA1 , BRCA2 , and PALB2 , is associated with sensitivity to platinum-based chemotherapy and PARP inhibition. Preclinical and clinical evidence suggest that combining PARP inhibition with immune checkpoint blockade may enhance antitumor activity. We therefore evaluated durvalumab, an anti–PD-L1 antibody, and olaparib, a PARP inhibitor, in patients with DDR-mutated mPC who had a favorable response to platinum-based chemotherapy. Methods: This phase II, open-label, single-arm, multicenter trial enrolled patients with mPC and BRCA1 , BRCA2 , or PALB2 -mutations who achieved a partial (PR) or complete response (CR) after platinum-based chemotherapy. Treatment consisted of oral olaparib (300 mg twice daily) plus intravenous durvalumab (1500 mg every 4 weeks) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by investigator assessment. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between Dec 2022 and Oct 2024, 40 patients were enrolled. The median age was 57.0 years (IQR 50-65), 52.5% were female, 82.5% had received ≥3 prior lines of chemotherapy, and 80% had mutations in BRCA2. At the data cut-off (July 2025), the median follow-up of 11.9 months. The ORR was 32.5% (13/40; CR: 1/40; PR: 12/40), with a median duration of response of 14.5 months. Median PFS was 6.7 months (95% CI, 3.7-NR), with a 24-month PFS rate of 22.0% (95% CI, 9.8-51.0). The DCR was 77.5% (31/40) and the median OS was 15.4 months (95% CI, 10.5-NR). The main efficacy outcomes are summarized in the Table. The most common treatment-emergent adverse events (TEAEs) were asthenia (37.5%), nausea (27.5%), and anemia (25%). Grade ≥3 TEAEs occurred in 37.5% of patients. Grade ≥3 treatment-related AEs occurred in 15% of patients, being anemia (10%) the main cause. Conclusions: Durvalumab plus olaparib demonstrated promising and durable antitumor activity, with a manageable safety profile, in patients with DDR-mutated mPC following platinum-based chemotherapy. Further research is needed to better identify patients with prolonged disease control. Clinical trial information: NCT05659914 . Outcome N=40 ORR, % (95% CI) 32.5% (19.1-49.2) Best response, n (%) CR 1 (2.5) PR 12 (30.0) SD 18 (45.0) PD 9 (22.5) Median PFS (95% CI) 6.7 mo (3.7-NR) 12-mo and 24-mo PFS rate 37% (25-56) and 22% (10-51) Median OS (95% CI) 15.4 mo (10.5-NR) Median DoR (95% CI) 14.5 mo (3.7-NR) CR, complete response; DCR, disease control rate; DoR, duration of response; NR, not reached; OS, overall survival; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response, SD, stable disease.
Florián et al. (2026) studied this question.