Efficacy of envafolimab combined with capecitabine and lenvatinib as postoperative adjuvant therapy for radical resected cholangiocarcinoma with high-risk recurrence factors: A phase II single-center prospective study.

e16289 Background: Surgery remains the cornerstone of curative treatment for cholangiocarcinoma. However, recurrence rates remain high (60-70%) even after R0 resection, particularly in high-risk patients This study aimed to evaluate the efficacy and safety of an adjuvant regimen combining capecitabine, lenvatinib, and envafolimab for high-risk patients following R0 resection of cholangiocarcinoma. Methods: This open-label, single-arm, phase II trial was conducted at the Sir Run Run Shaw Hospital. Patients with histologically confirmed R0-resected cholangiocarcinoma and at least one of high-risk features (e.g., lymph node positivity, nerve invasion, or vascular invasion) were consecutively enrolled. The treatment protocol included envafolimab (400 mg subcutaneous injection every three weeks for up to 35 cycles), capecitabine (oral administration of 1000 mg/m² for two weeks followed by one week off, every three weeks, without cycle limit), and lenvatinib (oral administration of 8 mg every three weeks for up to eight cycles). The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS) and safety. Results: Between July 2023 and May 2024, a total of 30 patients were recruited, with 28 included in the efficacy and safety analysis. As of January 2025, the median follow-up period was 16.9 months. Notably, the median DFS was observed to be 16.3 months, while the median OS data remain immature with a 1-year OS rate of 92.9%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with grade ≥3 TRAEs reported in 68%. Treatment discontinuation due to TRAEs affected 10% of participants, and no treatment-related mortalities were recorded. Conclusions: The combination of envafolimab, lenvatinib, and capecitabine demonstrated promising DFS with acceptable toxicity in the adjuvant setting for high-risk cholangiocarcinoma patients post R0 resection. These results highlight the potential of this therapeutic approach and warrant further investigation through randomized controlled trials. Clinical trial information: ChiCTR2300074241 .