Pucotenlimab

This is a prospective, open-label, single-arm phase II study designed to evaluate the efficacy and safety of FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) in combination with donafenib and pucotenlimab as first-line treatment in patients with unresectable intrahepatic cholangiocarcinoma.
Eligible patients will receive FOLFOX-HAIC administered every three weeks together with oral donafenib and intravenous pucotenlimab. Tumor response will be assessed according to RECIST v1.1. The primary objective of the study is to determine the objective response rate, and secondary objectives include progression-free survival, overall survival, disease control rate, and safety.

Study Design The study plans to enroll 38 patients. A Simon's two-stage design is employed. Based on historical data, the objective response rate (ORR) for patients meeting the inclusion criteria and receiving PD-1 inhibitor monotherapy is approximately 30%. The expected ORR for the combination of Pucotenlimab and Vebreltus is 55%. With a one-sided α=0.05 and 80% power, 9 patients will be enrolled in the first stage. If ≥2 patients achieve a partial response (PR) or complete response (CR), the study will proceed to the second stage. An additional 25 patients will be enrolled in the second stage, resulting in a total of 34 patients. If ≥15 patients in the total population achieve a PR, the study endpoint is considered met. Accounting for a 10% dropout rate, a total of 38 patients will be enrolled.
Study Procedures After providing full informed consent and passing screening, eligible subjects will receive treatment with Vebreltus 2.0 mg/kg and Pucotenlimab 200 mg. On the first day of each treatment cycle, patients will receive an intravenous infusion of Pucotenlimab (infusion duration: 60 min ± 15 min, with the first cycle infusion lasting no less than 60 minutes). At least 30 minutes after the completion of the Pucotenlimab infusion, the Vebreltus infusion will commence (infusion duration: 60 min ± 15 min, with the first cycle infusion lasting no less than 60 minutes). Patients will receive the combination therapy once every 3 weeks until completion of 2 years of treatment or until the occurrence of a protocol-defined treatment discontinuation event. Following the end of treatment, each subject will undergo a 30-day (+7 days) safety follow-up to monitor adverse events and clinically relevant events. Post-treatment survival follow-up will be conducted every 12 weeks (±7 days). For subjects who discontinue treatment for reasons other than disease progression/death and do not initiate new anti-cancer therapy, tumor imaging assessments will continue per the original schedule until disease progression, initiation of new anti-cancer therapy, withdrawal of consent, loss to follow-up, or death, whichever occurs first.
After enrollment, tumor response will be assessed according to RECIST v1.1 and iRECIST criteria. Imaging evaluations will be performed every 6 weeks (±7 days) from the first dose for the first 54 weeks, and then every 9 weeks (±7 days) thereafter (regardless of any delays in study drug administration), until iRECIST-confirmed progressive disease (iPD), initiation of new anti-cancer therapy, withdrawal of informed consent, loss to follow-up, or death, whichever occurs first.
Exploratory Analysis This study will analyze the correlation between biomarkers in patient tumor tissue/blood samples (e.g., EGFR expression, PD-L1 CPS score, TILs) collected before and after treatment and clinical efficacy endpoints (e.g., ORR, PFS, DoR).