Tislelizumab plus sitravatinib as adjuvant therapy for patients with hepatocellular carcinoma at high risk of recurrence after surgical resection: Preliminary analysis of a multi-center, non-randomized, open-label phase 2 study.

Abstract

e16239 Background: Adjuvant therapy has the potential to prevent or delay recurrence after curative-intent hepatectomy for hepatocellular carcinoma (HCC) patients. IMbrave 050 trial demonstrated improved recurrence-free survival (RFS) for HCC patients at high risk of recurrence when treated with atezolizumab plus bevacizumab, underscoring the promising potential of checkpoint inhibitor-based combination therapy as a strategy in the adjuvant setting. The aim of this study was to evaluate 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. Here, we reported the preliminary analysis results. Methods: HCC patients confirmed by histopathology or cytology, who had undergone a curative resection and with one or more of the high-risk factors for recurrence, including: a solitary tumor>5 cm, a solitary tumor>2cm and ≤5cm with microvascular invasion, or 2~3 lesions, were eligible. Enrolled 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 include 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 (86.4%) etiology, and 36.4% with microvascular invasion. Most patients were at BCLC stage A (86.4%), while stage 0 and stage B accounted for 4.5 and 9.1%, respectively. Till the data cut-off date on Nov. 30th, 2023, the median follow-up duration was 6.0 months (range 0.7-16.2); 2 patients relapsed and 1 patient died. The 1-year RFS rate was 81.3% and the longest RFS (censored) was over 12.5 months. Safety profile indicated that 21 patients (95.5%) experienced treatment-related adverse events (TRAEs), and 8 (36.4%) experienced grade ≥3 TRAEs. Most common (≥10%) grade ≥3 TRAEs were hypertension (13.6%) and palmar-plantar erythrodysesthesia (13.6%). Any grade immune-related adverse events (irAEs) were observed in 12 patients (54.5%) and 3 (13.6%) experienced grade ≥ 3 irAEs. AE leading to tislelizumab delay was observed in 2 patients (9.1%) and sitravatinb delay in 16 patients (72.7%). Dose reduction of sitravatinib occurred in 81.8% of patients due to AE. One patient died due to treatment-related pulmonary infection and biliary fistula. Conclusions: For patients with HCC at high risk of recurrence after curative-intent resection, tislelizumab plus sitravatinib showed preliminarily positive signal in controlling recurrence and had managable safety profile as adjuvant therapy. Further follow-up is needed to validate these findings with more mature data. Clinical trial information: NCT05407519 .