The goal of this clinical trial is to evaluate the efficacy and safety of AK112 combined with the GAP regimen as conversion therapy for patients with locally advanced gallbladder cancer who are initially considered unsuitable for curative surgery.
The main questions this study aims to answer are:
1. Whether AK112 combined with the GAP regimen can increase the rate of successful R0 radical resection after conversion therapy. 2. Whether this treatment approach can achieve tumor response and disease control with acceptable safety in patients with locally advanced gallbladder cancer.
Participants will receive AK112 combined with gemcitabine, cisplatin, and albumin-bound paclitaxel (GAP regimen) every 21 days for 4-6 treatment cycles. Tumor response will be evaluated by CT or MRI according to RECIST version 1.1 criteria. Patients who become eligible for surgery after multidisciplinary evaluation will undergo radical resection. All participants will be monitored for treatment-related adverse events, disease progression, and survival outcomes during follow-up.
Voluntarily provide written informed consent;
Age ≥18 years and ≤75 years at enrollment;
Histologically or cytologically confirmed gallbladder adenocarcinoma;
Radiological assessment meeting any of the following criteria: a. Hepatic invasion requiring extensive hepatectomy that the patient cannot tolerate; b. Biliary tract invasion extending beyond the bifurcation threshold requiring extensive hepatectomy that the patient cannot tolerate; c. Regional lymph node metastasis with fused bulky lymph nodes (maximum short-axis diameter >2 cm) compressing or invading critical blood vessels/biliary tracts, precluding radical lymphadenectomy; d. Primary tumor vascular invasion: main portal vein or left portal branch invasion without feasible vascular reconstruction; proper hepatic artery/common hepatic artery invasion >180°, or invasion <180% combined with mandatory portal vein reconstruction; right portal vein/right hepatic artery invasion with intolerance to extensive hepatectomy;e. Direct invasion of adjacent organs (pancreas, stomach, duodenum, colon);
Histological or cytological confirmation of gallbladder non-adenocarcinoma: squamous cell carcinoma, neuroendocrine neoplasm, lymphoma, sarcoma;
Presence of distant metastatic disease at screening;
Prior radiotherapy, chemotherapy, targeted therapy, or immunotherapy for gallbladder cancer;
Concurrent other malignant tumors besides gallbladder cancer;