A phase II/III study of camrelizumab plus apatinib as perioperative treatment of resectable hepatocellular carcinoma at intermediate-high risk of recurrence: Primary results of major pathologic response from phase II stage.

4126 Background: Surgical resection remains an important treatment strategy for patients (pts) with liver cancer. However, the 5-year recurrence rate is still 50-70% in surgically resectable pts. Intermediate-high risk factors of recurrence in HCC include single tumor size > 5 cm, multiple tumors, and microvascular invasion. The standardized perioperative regimen for resectable HCC has not been established. This study aimed to assess the efficacy and safety of camrelizumab plus apatinib (C+A) as a perioperative regimen in resectable HCC at intermediate-high risk of recurrence (Clinical trial: NCT04521153). Methods: In this multicentre, randomised, phase II/III study, eligible HCC pts (CNLC Ib-IIIa) were randomly assigned in a 1:1 ratio to treatment group and control group. Pts in treatment group received 2 cycles of C (200mg Q2W) plus A (250mg QD) followed by surgery and a post-surgical TACE. At least 6 cycles of sequential treatment of C (200mg Q3W) plus A (250mg QD) were performed after TACE. Pts in control group received surgical resection and a post-surgical TACE. Primary endpoint of phase III stage was 3-year EFS, of phase II stage was MPR (defined as less than 50% residual tumor) rate. In the phase II stage, futility analysis on a phase II outcome was performed after pts in treatment group completed surgical resection and pathological evaluation. If < 15% of pts achieved an MPR, or > 20% of pts had progression that precluded surgery, the study would not proceed to phase III stage. Results: In phase II stage, 60 pts were randomly assigned to treatment group, and 59 to control group. As of Nov 4, 2022, the last randomised pt underwent curatively surgical resection and pathological evaluation. The median age was 58 years (range, 21-75). 101(84.9%) were male, and 96 (80.7%) had HBV infection. In treatment group, 58 pts received neoadjuvant therapy, 52 completed 2 cycles of preoperative therapy and proceeded with planned resection. Surgery was aborted for 6 pts: 3 refused surgery, 2 deaths (1 for tumor rupture of HCC, 1 for immune related hepatitis), and 1 had protocol deviation. The MPR rates in the ITT population were 40% (24/60). Among them, 10% pts (6/60) had ≤ 5% surviving tumor cells in tumor bed. The MPR rate in pts who had surgical resection were 46.2% (24/52). 19.3% pts experienced ≥ 3 grade TRAEs, the most common of which were AST increased (5.3%), hypertension (5.3%), and ALT increased (3.5%). Conclusions: The phase II stage of the study did not meet the stopping criteria. Neoadjuvant camrelizumab plus apatinib therapy exhibits promising pathological response in HCC pts at intermediate-high risk of recurrence, with a tolerable safety profile. The phase III stage of the study is currently ongoing. Clinical trial information: NCT04521153 .