39TiP - A phase II study of tislelizumab (TIS) plus sitravatinib as adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risk of recurrence after surgical resection

Background

HCC recurs in 50%∼70% of patients within 5 years following potentially curative resection. Adjuvant therapies are expected to prevent early recurrence in high risk patients, however till now there is no solid evidence and consensus. The immune component of the liver microenvironment has been reported to play a key role in HCC recurrence. Sitravatinib is a selective tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MER) and split tyrosine-kinase domain-containing receptors (VEGFR2, KIT) that may help overcome the immunosuppressive tumor microenvironment and augment antitumor responses. TIS, an anti-PD-1 antibody, has shown encouraging and durable clinical antitumor activity in advanced HCC. An early trial showed that TIS plus sitravatinib was well-tolerated and had preliminary antitumor activity in previously treated advanced HCC. This open-label, multicenter, phase II study (NCT05407519) aims to evaluate the efficacy and safety of TIS plus sitravatinib as adjuvant therapy in patients with HCC at high risk of recurrence after curative resection.

Trial design

Eligible patients are aged from 18∼70 years and have HCC confirmed by histopathology or cytology; ECOG PS 0/1; Child-Pugh class A liver score; no prior systematic treatment and locoregional therapy; no invasion or tumor thrombus in portal vein, hepatic vein or bile duct and no extrahepatic metastasis or lymph node metastasis. Patients have undergone a curative resection, and those at high-risk of HCC recurrence will be eligible by fulfilling at least one of the following criteria: 1) a solitary tumor＞5 cm; 2) solitary tumor＞2cm and ≤5cm with microvascular invasion; and 3) 2∼3 lesions. Forty patients will receive TIS (200mg, IV, Q3W) combined with sitravatinib (100mg, PO, QD). TIS and sitravatinib will be administered until disease progression, intolerable toxicity, withdrawal of consent or death, with a maximum 17 cycles for TIS. Primary endpoint is 2-year recurrence-free survival (RFS) rate. Secondary endpoints include RFS, time to recurrence, overall survival (OS), 1-year RFS rate, 1-year and 2-year OS rate, and safety.

Clinical trial identification

NCT05407519.

Legal entity responsible for the study

The authors.

Funding

BeiGene, Ltd.

Disclosure

All authors have declared no conflicts of interest.