Adjuvant Sintilimab Plus Bevacizumab After Curative Resection of Spontaneously Ruptured Hepatocellular Carcinoma:...

Spontaneous rupture of hepatocellular carcinoma (srHCC) is a life-threatening complication associated with high perioperative mortality and increased postoperative recurrence, particularly peritoneal dissemination. Although timely haemostasis and curative-intent resection allow selected patients to achieve meaningful survival, postoperative management remains poorly defined, and patients with srHCC are usually excluded from major adjuvant trials.

CLEAR-2 is a prospective, exploratory, multicentre, single-arm study evaluating adjuvant sintilimab plus bevacizumab biosimilar after R0 resection of srHCC. Thirty-five patients with imaging- or intraoperatively confirmed spontaneous rupture, China Liver Cancer (CNLC) stage I-II disease, complete radiological response 4-8 weeks after surgery, ECOG performance status 0-1, Child-Pugh class A liver function, and adequate organ function will be enrolled. Preoperative transarterial embolisation for haemostasis is permitted as a single bridging procedure without chemotherapeutic agents, followed by surgery within 2 weeks. Treatment consists of sintilimab 200 mg plus bevacizumab biosimilar 15 mg/kg intravenously every 3 weeks for up to 1 year or until recurrence, unacceptable toxicity, or withdrawal. The primary endpoint is disease-free survival. Secondary endpoints include overall survival, safety, and recurrence patterns. Tumour assessments will be performed every 12 weeks using contrast-enhanced CT or MRI according to RECIST version 1.1.

CLEAR-2 is designed to generate preliminary prospective evidence on the feasibility, safety, and antitumour activity of adjuvant sintilimab plus bevacizumab in a highly selected, high-risk srHCC population. The findings may inform future randomized or comparative studies of postoperative strategies for srHCC.

NCT07331883.