Phase Ib/II clinical study of adebrelimab combined with decitabine, nab-paclitaxel, and gemcitabine as first-line (IL) treatment for metastatic pancreatic cancer (mPC).

4200 Background: Epigenetic enzyme inhibitors may synergize with immunotherapy by modulating antigen presentation and enhancing tumor-related gene expression. Preclinical studies suggest that low-dose decitabine can restore chemosensitivity in chemotherapy-resistant tumors. We conducted the Ib/II study to explore the efficacy and safety of decitabine combined with adebrelimab, nab-paclitaxel, and gemcitabine as 1L treatment for mPC. Methods: Eligible patients (pts) were prior untreated mPC or pts who had experienced disease progression more than six months after the end of postoperative adjuvant therapy. In the phase Ib, enrolled pts received dose escalation of decitabine (10 mg/m²/15 mg/m²,iv,d1-d3,q4w), adebrelimab (1200mg,iv,d1,q3w) , nab-paclitaxel (125 mg/m 2 , iv,d1,d8,d15,q4w), and gemcitabine (1000 mg/m 2 ,iv,d1,d8,d15,q4w) to determine the recommended phase 2 dose (RP2D) in a standard 3+3 design. In the phase II, pts received decitabine at the RP2D, adebrelimab, nab-paclitaxel and gemcitabine combination therapy. Primary endpoints were dose-limiting toxicities, RP2D, and objective response rate (ORR). Secondary endpoints included overall survival, progression free survival, disease control rate (DCR), duration of response, and safety. Results: From April 2024 to February 2025, 28 pts were enrolled and the median age was 62 yrs; 69.2% male, and 80.8% ECOG PS 1. The Ib phase established the RP2D of decitabine as 10 mg/m². Total of 22 pts were included in the efficacy analysis. The median follow-up was 11.9 mo. The ORR was 46% (10PR, 9SD, 3PD) and DCR was 86.4%. Median duration of response (mDoR) was 10.94 months, while the median progression-free survival (mPFS) was 6.47 months. 24 pts were analyzed for safety. The most common TRAEs of any grade were anemia (95.8%), lymphocyte count decreased (79.2%), hypoalbuminemia (75.0%), hyponatremia (75.0%), vomiting (66.7%). Grade ≥3 TRAEs were were anemia (25.0%), white blood cell decreased (20.8%), platelet count decreased (20.8%), lymphocyte count decreased (12.5%), neutrophil count decreased (12.5%). No new safety signals were observed. Conclusions: This study preliminarily demonstrates that the decitabine combination regimen has favorable efficacy and safety in 1L treatment of mPC. Future clinical studies with larger sample sizes are needed to be validated. Clinical trial information: NCT06454448 .