Efficacy of adebrelimab with chidamide, gemcitabine, and S-1 in locally advanced or metastatic pancreatic cancer: A phase II study.

Abstract

e16365 Background: Pancreatic cancer is an aggressive, immunologically “cold” tumor with an immunosuppressive microenvironment. Immune checkpoint inhibitors (ICIs), either alone or with chemotherapy, have shown disappointing results in advanced pancreatic cancer. Chidamide, a subtype-selective histone deacetylase inhibitor, enhances chemotherapy, immunotherapy, and endocrine therapy. Approved for peripheral T-cell lymphoma, diffuse large B-cell lymphoma, and hormone receptor-positive advanced breast cancer, chidamide also demonstrates efficacy in other tumor types. This ongoing study evaluates the efficacy and safety of combining adebrelimab with chidamide, gemcitabine, and S-1 as first-line therapy for locally advanced or metastatic pancreatic cancer. Methods: This prospective, single-arm, multicenter phase II trial included patients aged 18–75 with histologically confirmed locally advanced or metastatic pancreatic cancer, naïve to any therapy except biliary stenting, and with at least one measurable lesion. Patients received adebrelimab (1200 mg IV, D8), chidamide (20 mg PO, BIW, D8, 11, 15, 18), gemcitabine (800–1000 mg/m 2 IV, D1, 8), and S-1 (40–50 mg PO, BID, D1–14) on a three-week cycle. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR), and safety. Results: As of December 27, 2024, 13 patients were enrolled. The ORR was 62% (8/13), with a DCR of 92% (12/13). The median time to response was 1.66 months, with median PFS and OS of 9.0 and 14.2 months, respectively. CA199 levels decreased in patients with a tumor response; all with ≥40% reduction in CA199 had an objective response. Common treatment-related adverse events (AEs) included anemia, thrombocytopenia, leukopenia, hyperbilirubinemia, increased D-dimer, aspartate transferase levels, and lymphopenia. Grade ≥3 AEs occurred in 23% (3/13) of patients, including leukopenia (23%) and thrombocytopenia (15%). All AEs resolved with symptomatic treatment, and no patients withdrew due to AEs. Conclusions: Chidamide enhanced the efficacy of immunotherapy and chemotherapy, improving outcomes compared to chemotherapy alone or in combination with immunotherapy. The ADEPT regimen showed promising antitumor activity and favorable tolerability as first-line therapy for locally advanced or metastatic pancreatic cancer. Further data from a large cohort and longer follow-up will be presented. Clinical trial information: NCT06584227 . Efficacy data. PFS (m) OS (m) ORR (%) DCR (%) TTR (m) Median 9.0 14.2 62 92 1.66 95% CI 7.0–13.3 5.2–NE 31.58–86.14 63.97–99.81 1.43–1.99 CI, confidence interval; DCR, disease control rate; m, month; NE, not estimable; OS, overall survival; ORR, objective response rate; PFS, progression-free survival; TTR, time to response.