The purpose of this study is to explore the efficacy and safety of Ivonescimab in combination with GEMOX chemotherapy as neoadjuvant and conversion therapy for patients with biliary tract cancer. It aims to evaluate the impact of this combination regimen on postoperative recurrence, patient survival, and medication safety.
This is a single-center, phase II, interventional, single-arm, multi-cohort clinical study. A total of 87 eligible participants will be enrolled and assigned to either the neoadjuvant therapy cohort (45 participants) or the conversion therapy cohort (42 participants).
1. Subjects voluntarily participate in the study, agree to sign a written informed consent form, demonstrate good compliance, and are willing to cooperate with follow-up.
2. Male or female aged >= 18 and <= 80 years at the time of signing the ICF.
3. Histologically or cytologically confirmed biliary tract cancer (BTC, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer), and radiologically assessed as locally advanced or with oligometastases (defined as Stage IIIA or higher lesions according to the 8th edition of the AJCC staging system). Subjects must agree to provide archived or fresh tumor biopsy specimens and peripheral blood samples for biomarker testing.
Neoadjuvant Therapy Cohort: The tumor is graded as locally advanced with no distant metastasis, and theoretically can achieve radical resection through complex resection combined with vascular reconstruction, but both the surgical risk and postoperative recurrence risk are high (single tumor diameter > 5 cm; imaging suggests vascular invasion or hilar lymph node metastasis; tumor number > 3 or any single tumor > 3 cm; preoperative CA19-9 > 37 U/mL or exceeding the upper limit of normal [applicable to centers where the normal range is not < 37 U/mL]).
1. Diagnosed with mixed periampullary cancer, or mixed hepatocellular-cholangiocarcinoma.
2. Prior systemic anti-tumor therapy for BTC.
3. Prior treatment with gemcitabine-based chemotherapy, platinum-based chemotherapy, or any tumor immunotherapy/targeted therapy (e.g., PD-1/PD-L1 inhibitors, VEGF inhibitors, etc.).
4. History of severe allergy to other monoclonal antibodies. Known severe allergy or intolerance to gemcitabine, platinum drugs, or any of their components/excipients.
Single group
Ivonescimab
DrugAdministered at a dose of 20 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) in combination with GEMOX chemotherapy for 3 to 6 cycles. For eligible patients in the conversion therapy cohort who do not undergo surgery after evaluation, Ivonescimab is continued as maintenance monotherapy (20 mg/kg, IV, Q3W, Day 1) until disease progression, unacceptable toxicity, death, withdrawal of consent, or investigator decision.
GEMOX Regimen
DrugThe GEMOX regimen consists of Gemcitabine (1000 mg/m²) and Oxaliplatin (100 mg/m²). Both drugs are administered via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). This chemotherapy regimen is administered in combination with Ivonescimab for 3 to 6 cycles prior to surgical evaluation.
R0 Resection Rate
The proportion of participants in the neoadjuvant therapy cohort who undergo surgical resection and achieve microscopically margin-negative (R0) resection.
Objective Response Rate
The proportion of participants in the conversion therapy cohort achieving a Complete Response (CR) or Partial Response (PR) based on RECIST v1.1 criteria as assessed by investigators.
Objective Response Rate
The proportion of participants in the neoadjuvant cohort achieving CR or PR based on RECIST v1.1.
R0 Resection Rate
The proportion of participants in the conversion cohort who achieve resectability and obtain an R0 resection post-surgery.
Pathological Response Rate
The proportion of participants who achieve Major Pathological Response (MPR) or Pathological Complete Response (pCR) confirmed by postoperative pathology.
Disease Control Rate
The proportion of participants achieving CR, PR, or Stable Disease (SD) based on RECIST v1.1.
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Haitao Zhao, MD
Lead sponsor
Peking Union Medical College Hospital
Sponsor institution
