Exploring the Safety and Efficacy of Sacituzumab Tirumotecan Combined With Pucotenlimab in the Treatment of Advanced Cholangiocarcinoma
1. Primary Objectives (1) To evaluate the safety and tolerability of sacituzumab tirumotecan in combination with pucotenlimab in patients with advanced cholangiocarcinoma; (2) To assess the objective response rate (ORR) of sacituzumab tirumotecan combined with pucotenlimab in patients with unresectable or metastatic cholangiocarcinoma, as evaluated by investigators per RECIST v1.1; 2. Secondary Objectives (1) To evaluate the overall survival (OS) of sacituzumab tirumotecan combined with pucotenlimab in advanced cholangiocarcinoma; (2) To assess progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), and time to response (TTR) in patients treated with sacituzumab tirumotecan combined with pucotenlimab, as determined by investigators based on RECIST v1.1; (3) To further evaluate PFS (as a standalone secondary endpoint); 3. Exploratory Objectives (1) To investigate the correlation between TROP2 expression, systemic immune biomarkers, and treatment efficacy.
• 1\. Age \>= 18 years old; 2. Histologically confirmed unresectable or metastatic cholangiocarcinoma (including gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma)
• (1) First line treatment cohort:
⁃ Patients who explicitly refuse chemotherapy;
⁃ Patients who fail adjuvant therapy with chemotherapy;
⁃ Patients who have not received systemic therapy; (2) Second line treatment cohort:
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‣ First line chemotherapy is effective, but toxicity is not tolerated;
⁃ Disease progression after first-line chemotherapy regimen\]; 3. Patients with positive TROP2 protein; 4. The patient is a patient with distant metastasis or locally advanced stage who cannot undergo surgery or radiotherapy and has not received systemic treatment; 5. According to RECIST 1.1 tumor evaluation criteria, there is a measurable primary lesion; 6. No active autoimmune diseases; 7. No concurrent malignant tumors; 8. ECOG physical fitness score 0-1; 9. Expected survival period \>= 3 months; 10. Having sufficient organ and bone marrow function (not receiving blood transfusions, recombinant human thrombopoietin or colony-stimulating factor therapy within 2 weeks prior to the first administration), defined as follows:
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‣ Blood routine: neutrophil count (NEUT) \>= 1.2 × 10\^9/L; platelet count (PLT) \>= 75 × 10\^9/L; hemoglobin \>= 9 g/dL;
⁃ Liver function: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) \<= 2.5 x upper limit of normal (ULN); Total bilirubin (TBIL) \<= 1.5 × ULN; If there is liver metastasis, ALT and AST should be \<= 5ULN;
⁃ Renal function: plasma Cr \<= 1.5ULN or creatinine clearance rate (Ccr) \>= 60 ml/min (for males: GFR (ml/min)=(140 age) x body weight (kg) x 0.85/blood creatinine (mg/dl); For women: GFR (ml/min)=(140 age) x body weight (kg) x 0.85 x 0.85/blood creatinine (mg/dl);
⁃ Coagulation function: International normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) \<= 1.5 × ULN; 11. For female subjects with fertility and male subjects with reproductive potential partners, they must agree to take effective medical contraceptive measures within 6 months from the signing of the informed consent form until the last administration; 12. Voluntarily join this study and sign an informed consent form. If the subject is unable to read and sign the informed consent form due to reasons such as lack of capacity, their guardian needs to act as a proxy for the informed process and sign the informed consent form. If the subject lacks the ability to read the informed consent form (such as illiterate subjects), a witness is required to witness the informed process and sign the informed consent form.