A phase II, single-arm, exploratory study of GEMOX combined with tislelizumab and donafenib in the perioperative treatment of potentially resectable intrahepatic cholangiocarcinoma with high recurrence risk.

TPS11199 Background: Biliary tract cancer (BTC) is characterized by strong invasiveness and poor prognosis, with a metastasis and recurrence rate of up to 67% within 1 year after surgery and a 5-year overall survival rate of only 5%~15%. Among BTC subtypes, intrahepatic cholangiocarcinoma (ICC) accounts for a relatively high proportion, and its unique biological behaviors result in persistently high postoperative recurrence risk, which seriously endangers patients' life and health. Currently, major guidelines recommend that patients with potentially resectable ICC at high recurrence risk participate in clinical trials to explore optimal treatment strategies. For patients evaluated as "technically resectable but with high-risk recurrence" before surgery, clinical practice has shown that neoadjuvant therapy can effectively eliminate micrometastases and reduce the difficulty of R0 resection; postoperative adjuvant therapy can further prevent recurrence. Therefore, we innovatively propose a perioperative treatment model aimed at breaking through the existing therapeutic predicament. Methods: This study is a phase Ⅱ, single-arm, exploratory study with a fixed sample size of 20 patients. The inclusion criteria are intrahepatic cholangiocarcinoma (ICC) (TNM stage T1-4, N0-1, M0)based on preoperative assessment, initial technical resectability per imaging, and at least one high - risk recurrence factor. High-risk recurrence factors include: tumor diameter >5 cm, regional lymph-node positivity, satellite/multifocal lesions, radiological suspicion of diaphragmatic adhesion, CA19-9 >200 U/ml, and an anticipated surgical margin <1 cm on pre-operative imaging. Treatment involves two 21 - day cycles of GEMOX (gemcitabine 1000mg/m² on day 1 and 8, oxaliplatin 100mg/m² on day 1) with tislelizumab (200mg on day 1) and donafenib (0.2g orally twice daily). If investigators confirm patients meet surgical criteria (R0 resection expected), surgery follows 1 - 2 weeks post - treatment. Post - surgery, adjuvant therapy starts within 5 weeks. The regimen is capecitabine (1250mg/m² orally twice daily on days 1 -14) or S - 1 (40 -60mg orally twice daily on days 1 -14, weight - adjusted) plus tislelizumab (200mg on day 1) and donafenib (0.2g orally twice daily), repeated every 21 days for six cycles. Primary endpoint is event - free survival (EFS). Secondary endpoints are objective response rate (ORR) and disease control rate (DCR) per RECIST1.1, R0 resection rate, major pathological response rate(MPR, the proportion of patients who underwent radical surgery and had ≤10% residual viable tumor in the postoperative specimen), treatment completion rate, overall survival (OS), disease - free survival (DFS), and safety (treatment - related adverse events' incidence and severity). Clinical trial information: ChiCTR2500112067.