Envafolimab and chidamide in combination with GEMOX as first-line treatment for advanced and metastatic biliary tract cancer (B-Enefits/SCOG-B001): A single-arm, exploratory, phase 2 trial.

e16231 Background: Biliary tract cancer (BTC) is a rare malignant tumor with poor prognosis. Envafolimab is a light-chain deficient PD-L1 antibody. Chidamide is a subtype-selective histone deacetylase (HDAC) inhibitor. Here we conducted a single-arm, multicenter, prospective phase Ⅱclinical study (ChiCTR2400080783) to evaluate the efficacy and safety of Envafolimab and Chidamide in combination with GEMOX as first-line treatment. Methods: Patients with advanced BTCs receive treatment of Envafolimab (400 mg, on day 1) and Chidamide (20 mg orally for twice a week, on day 0, 3, 7, and 10), and GEMOX (gemcitabine 1000 mg/m 2 , on day 1 and 8, and oxaliplatin 100 mg/m 2 , on day 1) every 3 weeks for 8 cycles, followed by maintenance treatment with Envafolimab, Chidamide, and gemcitabine until PD, unacceptable toxicity, or patient refusal. The primary end points are safety and ORR. The secondary end points include PFS, OS, DCR, QoL and nutrition score. Results: From Feb 2023 to December 2024, a total of 35 patients were enrolled, including 29 patients with cholangiocarcinoma and 6 patients with gallbladder cancer. The median age was 67 years (range, 33-79). The ORR and DCR were 51.43%(18/35) and 77.14%(27/35) respectively. The median PFS was 8.13 months(95%CI, 2.338-13.922), and the median OS had not been reached. The overall incidence of Treatment-related adverse events（TRAEs）was 100% (all grades) and 68.57%（grade 3-4）. The most frequent grade 3-4 TRAEs included decreased platelet count (48.57%, 17/35), anemia (37.14%, 13/35), and leukopenia (37.14%, 13/35). No treatment-related deaths were reported. Conclusions: The combination of Envafolimab, Chidamide, and GEMOX demonstrated promising efficacy and tolerable adverse reactions in patients with advanced BTC. Clinical trial information: ChiCTR2400080783 .