What type of study is this?

This is a Pre-Registered Trial study.

What question did this study set out to answer?

Assess antitumor activity of durvalumab plus olaparib in metastatic pancreatic cancer with DNA damage repair gene alterations.

January 14, 2026

Phase II study of durvalumab plus olaparib in patients with metastatic pancreatic cancer and DNA damage repair gene alterations.

Key Points

Assess antitumor activity of durvalumab plus olaparib in metastatic pancreatic cancer with DNA damage repair gene alterations.
Phase II, open-label, single-arm, multicenter trial
Enrolled patients with mPC and BRCA1, BRCA2, or PALB2 mutations
Administered olaparib with durvalumab until progression or toxicity
Objective response rate was 32.5% with 1 complete response and 12 partial responses
Median progression-free survival was 6.7 months
Safety profile was manageable with common adverse events including asthenia and anemia

Abstract

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.

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