A Multicenter Phase 1b/2 Trial Investigating the Efficacy and Toxicity of the Combination of Gemcitabine, Cisplatin, Nab-Paclitaxel, and Tislelizumab in Treatment Naïve Patients With Unresectable, Locally Advanced, or Metastatic BTC
This is a multicenter Phase 1b/2 clinical trial investigating the efficacy and safety of a combination regimen of Gemcitabine, Cisplatin, Nab-paclitaxel, and Tislelizumab in treatment-naïve patients with unresectable, locally advanced, or metastatic biliary tract cancers (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer. The Phase 1b portion aims to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of Nab-paclitaxel in combination with Gemcitabine, Cisplatin, and Tislelizumab. In the Phase 2 portion, the study will evaluate the Objective Response Rate (ORR) as the primary endpoint, with additional assessments of Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), and Quality of Life (QoL). Safety and tolerability will also be closely monitored. This study seeks to leverage the stromal-disrupting effect of Nab-paclitaxel and the immune checkpoint blockade effect of Tislelizumab, combined with the established chemotherapy backbone of Gemcitabine and Cisplatin, to enhance treatment outcomes for BTC patients. The study will enroll patients across three medical centers in South Korea, including CHA Bundang Medical Center, Haeundae Paik Hospital, and Seoul National University Bundang Hospital.
• Histologically confirmed biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer (excluding neuroendocrine tumors, sarcoma, mixed cholangiocarcinoma-HCC, and ampullary carcinoma).
• Age ≥ 19 years at the time of signing informed consent.
• Treatment-naïve for unresectable or metastatic BTC, or recurrence/metastasis at least 6 months after curative surgery or adjuvant chemotherapy.
• Measurable lesions per RECIST v1.1.
• ECOG Performance Status (PS) of 0-1 within 14 days prior to the first dose.
• Life expectancy of ≥ 3 months.
• Adequate organ function (within 14 days prior to the first dose):
‣ Hematologic function: Hemoglobin (Hb) ≥ 9.0 g/dL, Absolute neutrophil count (ANC) ≥ 1,500/μL, Platelet count ≥ 100,000/μL
⁃ Renal function: Serum creatinine ≤ 1.5 × ULN or CrCl (Cockcroft-Gault) ≥ 45 mL/min
⁃ Hepatic function: AST and ALT ≤ 3.0 × ULN (≤ 5.0 × ULN for hepatic metastases), Total bilirubin ≤ 1.5 × ULN
⁃ Coagulation: INR ≤ 1.5 or prothrombin time ≤ 1.5 × ULN, aPTT ≤ 1.5 × ULN
• Reproductive status:
‣ Female participants must provide proof of non-childbearing status or a negative serum pregnancy test within 7 days before the first dose.
⁃ Female subjects receiving cisplatin must agree to effective contraception for 14 months after the last dose; male subjects must agree for 11 months.
⁃ Women of childbearing potential and non-sterilized men must use at least two effective contraceptive methods during the study and for 6 months after the last dose.
• Cardiac function:
‣ Left ventricular ejection fraction (LVEF) ≥ 50% (by echocardiography or MUGA scan)
⁃ No serious valvular disorders or arrhythmias
⁃ Corrected QT interval ≤ 470 msec at screening
• Willingness to provide tumor tissue samples by biopsy (endoscopic or excisional).