Tislelizumab and sitravatinib as adjuvant therapy for hepatocellular carcinoma patients at high risk of recurrence following surgical resection: A multi-center, non-randomized, open-label phase 2 study.

e16282 Background: Hepatocellular carcinoma (HCC) has a high risk of recurrence after resection. The IMbrave 050 trial suggested that adjuvant atezolizumab plus bevacizumab might delay recurrence-free survival (RFS) in patients with resected or ablated hepatocellular carcinoma with high-risk of recurrence, highlighting the benefits of checkpoint inhibitor combining anti-angiogenesis agent in preventing or delaying recurrence after curative resection. This study evaluated the efficacy and safety of tislelizumab (a PD-1 inhibitor) plus sitravatinib (a selective tyrosine kinase inhibitor) as adjuvant therapy in HCC patients at high risk of recurrence after curative-intent hepatectomy (NCT05407519). Methods: Eligible patients had histopathology or cytology confirmed HCC, underwent curative resection, and presented with one or more high-risk factors for recurrence, including: a solitary tumor＞5 cm, a solitary tumor＞2cm and ≤5cm with microvascular invasion, or 2~3 lesion. Patients received tislelizumab (200mg, IV, Q3W) and sitravatinib (100mg, PO, QD), with a maximum treatment duration of one year. The primary endpoint was 2-year RFS rate. Secondary endpoints included RFS, time to recurrence, overall survival (OS), 1-year RFS rate, 1-year and 2-year OS rate, and safety. Results: A total of 22 patients were enrolled, with hepatitis B being the most common etiology (86.4%). The majority of patients were at BCLC stage A (86.4%). Stages 0 and B accounted for 4.5% and 9.1%, respectively. Nearly one third of patients (31.8%) had microvascular invasion. As of Nov 19, 2024, the median study follow-up was 14.6 months. None of patients remained on study treatment. The median treatment duration of tislelizumab and sitravatinib was 298.5 days (IQR, 185.0-357.0) and 287.0 days (IQR, 151.0-357.0) respectively. The 2-year RFS rate (primary endpoint) was not mature. The median RFS was not reached (95% CI, 10.5 to not estimable), with 1-year RFS rate of 73.1% (95% CI, 46.8-87.9). The safety profile indicated that 21 patients (95.5%) experienced treatment-related adverse events (TRAEs), and 9 (40.9%) experienced grade ≥3 TRAEs. Immune-related adverse events (irAEs) of any grade were observed in 15 patients (68.2%) and 4 (18.2%) experienced grade ≥ 3 irAEs. TRAEs led to tislelizumab discontinuation in 1 patient (4.5%) and sitravatinib discontinuation in 5 patients (22.7%). Treatment-related pulmonary infection and biliary fistula led to the death of one patient. Conclusions: Tislelizumab plus sitravatinib yielded clinically promising efficacy and had manageable safety profile as adjuvant therapy in HCC patients with high risk of recurrence. Continued follow-up is ongoing to assess the long-term efficacy and safety of this combination strategy. Clinical trial information: NCT05407519 .