711P Sintilimab combined with bevacizumab biosimilar as a conversion therapy in potentially resectable intermediate stage hepatocellular carcinoma (HCC): A phase II trial

The combination treatment using sintilimab (a PD-1 antibody) and bevacizumab (bev) biosimilar improved PFS and OS in unresectable or advanced HCC as compared with sorafenib in ORIENT-32 study and was approved as first-line treatment for unresectable HCC in China. We assessed the efficacy and safety of the combination therapy as conversion therapy for potentially resectable intermediate stage HCC. Treatment-naïve patients (pts) with potentially resectable intermediate stage (BCLC stage B) HCC were enrolled in this phase II trial (NCT04843943). Eligible pts received sintilimab (200 mg, IV, D1) and bev (15 mg/kg, IV, D1) per 3 weeks. Tumor response and resectability were assessed every 6 weeks per RECIST v1.1. Pts with evaluations of PR or at least two SD and eligible for R0 resection were referred for hepatectomy, then continued with sintilimab/bev for at most 12 months. Primary endpoints were event-free survival (EFS) and treatment safety. Key secondary endpoints included R0 resection rate, pathologic response, objective response rate (ORR), and disease control rate (DCR). At data cutoff on April 26, 2022, 30 pts with BCLC-B stage HCC were enrolled. Of them, 25 pts (83.3%) were up-to-7 criteria out. The median follow-up time was 7.0 months (range 3.2–13.1). All pts completed at least one imaging evaluation. ORR and DCR were 23.3% and 90% (7 PR and 20 SD). 13 pts (43.3%) met the pre-designated criteria for hepatectomy and received liver resection, including 5 were evaluated as PR and 8 as SD before surgery. The median time from initiation of sintilimab/bev to liver resection was 4.1 months (range 2.0-5.7). No postoperative mortality was observed. 1 patient had a pathological complete response. Median EFS data was still not mature. There is no tumor recurrence in patients with hepatectomy for now. Most treatment-related AEs (TRAE) were grade 1-2, Grade 3 TRAEs occurred in 6 pts. 3 serious adverse events occurred, and 1 was treatment associated (rash). Systemic therapy using Sintilimab/bev as conversion therapy for intermediate-stage HCC was well tolerated and effective. Longer follow up are required to further evaluate the efficacy and safety.