Protocol of notable-HCC: a phase Ib study of neoadjuvant tislelizumab with stereotactic body radiotherapy in patients with resectable hepatocellular carcinoma

INTRODUCTION: Liver resection is the mainstay of curative-intent treatment for hepatocellular carcinoma (HCC), but the postoperative 5-year recurrence rate reaches 70%, and there are no adjuvant or neoadjuvant therapies recommended by major HCC guidelines that can reduce the risk of recurrence. In the recent decade, significant progress has been achieved in the systemic treatment of HCC, mainly from immune checkpoint inhibitors (ICIs) and targeted therapy. In other malignancies, ICIs in the neoadjuvant setting have shown better outcomes than in the adjuvant setting. On the other hand, the addition of radiation to ICIs incrementally improves the systemic response to ICIs. Neoadjuvant therapy of ICIs plus stereotactic body radiotherapy (SBRT) has shown promising results in several types of solid tumours but not HCC. METHODS AND ANALYSIS: Here, we describe a phase Ib clinical trial of neoadjuvant SBRT plus PD-1 (tislelizumab) prior to hepatic resection in HCC patients. Prior to resection, eligible HCC patients will receive 8 Gy×3 fractions of SBRT together with two cycles of tislelizumab with an interval of 3 weeks. HCC resection is scheduled 4 weeks after the second dose of tislelizumab, followed by adjuvant tislelizumab for 1 year. We plan to enrol 20 participants in this trial. The primary study endpoints include the delay of surgery, tumour response and safety and tolerability of the sequential SBRT/tislelizumab. Other endpoints are the disease-free survival and overall survival rates every 3 or 6 months after the surgery. ETHICS AND DISSEMINATION: This trial was approved by the Ethics Committee of Shandong Cancer Hospital and Institute (SDZLEC2022-021-01). The final results of this trial will be published in a peer-reviewed journal after completion. TRIAL REGISTRATION NUMBER: NCT05185531.