Neoadjuvant Tuvonralimab and Iparomlimab With Gemcitabine-oxaliplatin for Biliary Tract Cancer
The goal of this clinical trial is to learn if Tuvonralimab/Iparomlimab-based neoadjuvant regimens can improve surgical and pathological outcomes in adults (≥18 years) with resectable or borderline-resectable biliary tract cancer (intrahepatic/extrahepatic cholangiocarcinoma or gallbladder cancer), ECOG 0-1, and no prior neoadjuvant therapy. The main questions it aims to answer are: 1. Does the regimen increase the R0 resection rate (negative margins)? 2. Does it raise major or pathologic complete response rates (MPR/pCR) and improve event-free survival (EFS) without increasing perioperative complications? Researchers will compare Tuvonralimab/Iparomlimab-based therapy + GEMOX chemotherapy to surgery to see if immunotherapy leads to higher R0 resection, deeper pathologic response, and better EFS/PFS/OS with acceptable safety. Participants will: Undergo baseline assessments: imaging (contrast-enhanced CT/MRI ± PET), labs, histology, and optional biomarker sampling. Receive neoadjuvant therapy: 2-4 cycles (\\ 6-12 weeks) of a Tuvonralimab/Iparomlimab-based regimen per protocol. Have restaging by RECIST 1.1; eligible participants proceed to curative-intent surgery with central review of margins and tumor regression grading (TRG/MPR/pCR). Receive protocol-directed postoperative management and safety monitoring (CTCAE v5.0) and be followed every 8-12 weeks for EFS, PFS, OS, conversion-to-resection rate, nodal down-staging, perioperative complications, length of stay, and any surgery delays.
• The subjects voluntarily participated in the study and agreed to sign the written informed consent. They had good compliance and cooperated well with the follow-up.
• At the time of signing the informed consent form, the applicant was over 18 years old and could be of any gender.
• Patients with bile duct cancer diagnosed by histological or imaging methods, and whose imaging assessment or clinical assessment indicates borderline resectability
• There is at least one measurable lesion (as per the RECIST 1.1 criteria, this measurable lesion must have a spiral CT scan diameter of ≥ 10mm or the short diameter of a swollen lymph node of ≥ 15mm)
• Patient has not received any systematic treatment in the past
• The patient has locally advanced disease but no distant metastasis. Theoretically, a R0 resection can be achieved through complex resection combined with vascular reconstruction, but the risk is high.
• One of the following situations exists: 1. The main portal vein or a long segment of the hepatic artery on one side is affected, while the other side is still capable of supplying blood or draining. Vascular angioplasty or reconstruction can be performed. 2. The tumor involves the bile duct area beyond one secondary branch, but does not affect the primary branch on the opposite side. It is expected that the available residual liver and bile duct drainage can still be retained. 3. There is suspected regional lymph node metastasis (at the hepatic hilum, abdominal cavity), but there is no distant lymph node or peritoneal implantation.
• The ECOG score was 0-1 within one week before enrollment.
• The hematology and organ functions are adequate. Based on the laboratory test results obtained within 14 days prior to the start of the treatment (unless otherwise specified): Blood routine examination: (No blood transfusion, no use of G-CSF, no use of drugs for correction within 14 days before screening): Hb ≥ 90 g/L; Neutrophils ≥ 1.5 × 109/L; PLT ≥ 100 × 109/L. Biochemical examination: (No albumin transfusion within 14 days): Appropriate liver function: ALT and AST ≤ 2.5 × ULN; Bilirubin ≤ 2.0 × upper limit of normal; Appropriate renal function: Creatinine ≤ 1.5 × ULN, or creatinine clearance rate (CCr) \> 50 mL/min (using the standard Cockcroft-Gault formula)
• Fertile women: Agree to abstain from sexual intercourse (avoiding heterosexual intercourse) during the treatment period and for at least 6 months after the last administration (or use a contraceptive method with a failure rate of less than 1% for contraception)
• Men agree to abstain from sexual intercourse (not having sex with the opposite sex) or to use contraceptive measures, and agree not to donate sperm.