An Exploratory Study Of Sorafenib Plus Toripalimab For Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus.

TPS4658 Background: Portal vein tumor thrombosis (PVTT) is common among advanced hepatocellular carcinoma ( HCC), resulting in poor prognosis. As the standard first-line treatment, the efficacy of Sorafenib is not satisfactory in HCC with PVTT. Although immune checkpoint inhibitors have made a breakthrough in treatment of advanced HCC, objective response rate (ORR) of anti-PD-1 monoclonal antibody monotherapy is only 17-20%. Recently, PD-1/PD-L1 inhibitors combined with anti-angiogenesis therapy have shown good efficacy in the clinical studies. However, the data on immunotherapy for HCC with PVTT are still limited. Toripalimab is the first Chinese-produced anti-PD-1 monoclonal antibody marketed. We designed the study to evaluate the efficacy and safety of Sorafenib plus Toripalimab as the first-line treatment for unresectable HCC with PVTT. Methods: The study is a multicenter, single-arm, phase Ib/II trial. The primary objectives are 6-month progression-free survival (PFS) rate and safety. Secondary objectives include ORR, disease control rate, PFS, overall survival. The escalation stage includes two dose cohorts: Sorafenib 400 mg po qd or 400 mg bid combined with Toripalimab 240 mg iv d1 q3w. 6-12 patients are estimated to evaluate the dose-limiting toxicity within the first 42 days of administration. In the expansion stage, patients are treated with the recommended dose based on the escalation stage, until progressive disease or intolerable toxicity. Assuming Sorafenib plus Toripalimab can improve the 6-month PFS rate to 40% (Sorafenib:20%, β = 0.2, α = 0.05) and dropout is 10%, this stage need 39 patients. A total of 45-51 patients are enrolled. Major eligibility requirements include: unresectable HCC with diagnoses confirmed histologically or cytologically, or confirmed clinically in accordance with Chinese guideline for HCC diagnosis and treatment (v2017); radiographic evidence of PVTT; age ≥18 and < 75 years; at least one measurable lesion according to RECIST 1.1; a predicted life expectancy ≥ 3 months; ECOG PS≤1, Child-Pugh class A or B (≤7); no any prior systemic anti-cancer treatment; adequate organ function. Patients with hepatitis B treated with antiviral therapy (viral load < 100 IU/mL) or patients with chronic hepatitis C can be included. The study is open and actively enrolling at time of submission. Clinical trial information: NCT04069949 .