Iparomlimab and Tuvonralimab Injection Combined With GemOX and Lenvatinib as Conversion Therapy for Initially Potentially Resectable Intrahepatic Cholangiocarcinoma and Gallbladder Cancer

This single-arm, single-center clinical study aims toevaluate the efficacy and safety of Iparomlimab and Tuvonralimab Injection (QL1706, an Anti-PD-1/CTLA-4 Combined Antibody) combined with GemOX and lenvatinib as conversion therapy for Initially Potentially Resectable intrahepatic cholangiocarcinoma and gallbladder cancer. This study consists of three phases: screening, treatment, and follow-upEfficacy evaluation and safety monitoring should be performed throughout the study.

Inclusion criteria

• Age ≥ 18 years, male or female.
• Histologically or cytologically confirmed diagnosis of locally advanced or potentially resectable intrahepatic cholangiocarcinoma or gallbladder cancer, defined as T2b-T4 or N1 M0 according to the AJCC 8th edition.
• Expected life expectancy ≥ 12 weeks.
• No prior systemic treatment for biliary tract cancer before the first dose of study medication.
• At least one measurable lesion as defined by RECIST 1.1 criteria.
• ECOG Performance Status of 0 or 1.
• Adequate organ function, without severe dysfunction of the hematologic, cardiac, pulmonary, hepatic, renal, bone marrow, or immune systems.
• Laboratory tests meeting the following requirements: Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days before enrollment and voluntarily use adequate contraception during the observation period and for 8 weeks after the last dose of the study drug. For men, they must be surgically sterile or agree to use adequate contraception during the observation period and for 8 weeks after the last dose of the study drug.
• Patient voluntarily participates and provides written informed consent.
• Good compliance is anticipated, allowing for efficacy and adverse event follow-up per the protocol.

Exclusion criteria

• The subject has received any prior antitumor therapy or any investigational anticancer agents.
• Presence of any active autoimmune disease or a history of autoimmune diseases (e.g., interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism [may be enrolled if stable on hormone replacement therapy]). Patients with childhood asthma that has completely resolved in adulthood without any intervention, or vitiligo, may be enrolled. Patients requiring medical intervention with bronchodilators are not eligible.
• Known congenital or acquired immunodeficiency, such as Human Immunodeficiency Virus (HIV) infection.
• Uncontrolled cardiac clinical symptoms or diseases, e.g., NYHA Class II or above heart failure, unstable angina, myocardial infarction within 1 year, or patients with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.
• Severe concurrent infection within 4 weeks prior to the first dose (e.g., requiring intravenous antibiotics, antifungals, or antivirals), or unexplained fever >38.5°C during screening/prior to the first dose.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Administration of a live attenuated vaccine within 4 weeks prior to the first dose or planned administration during the study period.
• History of or concurrent other malignant tumors within the past 5 years (except for adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, and ovarian cancer).
• Gastrointestinal bleeding event or active hemoptysis within 28 days prior to the first dose.
• Gastric or esophageal varices requiring treatment.
• Active malignant tumors within 36 months prior to enrollment.
• Known allergy to any of the investigational drug components.
• Poorly controlled psychiatric disorder.
• Presence of superior mesenteric vein tumor thrombus, metastasis to group 16 lymph nodes, or distant metastasis to other organs / biological factors: peritoneal metastasis, direct invasion to adjacent organs, etc. / involvement of organs (pancreas, stomach, duodenum, colon) that cannot be resected en bloc.
• Any other condition deemed by the investigator as unsuitable for enrollment. This includes, but is not limited to, pre-existing central nervous system metastases, severe laboratory abnormalities, or familial/social factors that could compromise the subject's safety, or data/sample collection.
• Patients with extensive liver metastases involving the entire liver.