Chidamide plus envafolimab combined with S-1 as second-line treatment in advanced and metastatic pancreatic cancer (P-henomS/SCOG-P002): A single-arm, exploratory, multicenter, phase 2 trial—Interim report.

740 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with poor prognosis worldwide. Chidamide, a subtype-selective histone deacetylase (HDAC) inhibitor, has significant anti-tumor effects and extensive synergistic effects with immunotherapy. Envafolimab is a light-chain deficient PD-L1 antibody. Here we conducted a single-arm, multicenter, prospective phase Ⅱ clinical study (ChiCTR2200058431) to evaluate the efficacy and safety of Chidamide plus Envafolimab combined with S-1 as second-line treatment in advanced and metastatic pancreatic cancer. Methods: Patients with metastatic PDAC receive Envafolimab (400 mg, on day 1), Chidamide (20 mg orally twice weekly, on days 0, 3, 7, and 10), and S-1 (40-60 mg according to body surface area, orally twice daily from day 1 to 14) every 3 weeks until disease progression, unacceptable toxicity, or patient refusal. The primary end points are safety and ORR. The secondary endpoints were PFS, OS, DCR, QoL and nutrition score. Results: Recruitment completed with 16 patients as of September 2023 and the data cut-off for analysis was August 2024, 13 were evaluable. Median age was 66 (range 59 - 80), with 5 males and 11 females. After a median follow-up of 8.5 months, the ORR and DCR by RECIST v1.1 were 30.77% and 76.92%, respectively. Median PFS was 5.83 months (95%CI 2.592-9.068) and median OS was not reached. No new safety signals were observed. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 31.25% of patients. The most common TRAEs were anemia (12.5%), decreased platelet count (6.25%) and neutropenia (12.5%). No treatment-related deaths occurred. Conclusions: Preliminary data suggest that Chidamide and Envafolimab in combination with S-1 may be an effective second-line treatment with a manageable safety profile for patients with PDAC. Clinical trial information: ChiCTR2200058431 . Efficacy evaluation. Efficacy Evaluation AII (N = 13) n(%) Best efficacy evaluation Partial Response (PR) 4（30.77%） Stable Disease (SD) 6（46.15%） Progressive Disease (PD) 3（23.08%） Objective response rate (ORR) 30.77% 95%CI 9.09-61.43 Disease control rate (DCR) 76.92% 95%CI 46.19-94.96 mPFS（95%CI） 5.83（2.592-9.068） mOS（95%CI） -（NR）