90P - HAIC plus sintilimab and bevacizumab biosimilar as treatment for patients with advanced hepatocellular carcinoma (HCC): a phase II trial

Background

The combination treatment using sintilimab (a PD-1 antibody) and bevacizumab (bev) biosimilar demonstrated excellent efficacy and safety in ORIENT-32 study and HAIC performed impressive tumor response in researches. We assessed the efficacy and safety of the combination therapy as first-line treatment for initial unresectable HCC.

Methods

The study was an ongoing open-label, single-arm, phase II trial. Treatment-naïve HCC patients (pts) with initial unresectable and BCLC stage B or C were enrolled in this phase II trial. Eligible pts received sintilimab (200 mg, IV, D1) and bev (15 mg/kg, IV, D1) per 3 weeks, as well as FOLFOX-HAIC per 3-6 weeks. Pts eligible for resection were referred for hepatectomy after bev weaned over at least a 4-week period. Sintilimab and bev were given until disease progression or unacceptable toxicity or up to 24 months, and FOLFOX-HAIC were given 3-6 times. Primary endpoints were progression-free survival (PFS) per RECIST v1.1 and key secondary endpoints included objective response rate (ORR), disease control rate (DCR), surgical conversion rate, pathologic response, overall survival (OS) and safety.

Results

At data cutoff on July 25, 2023, 43 pts were enrolled, 41 of them underwent at least one course of treatment and 38 enrollees received at least one tumor assessment. The median follow-up time was 6.34 months (range 0.2–14.62). mPFS and mOS were not reached. According to RECIST v1.1, ORR and DCR were 68.42% and 100% (26 PR and 12 SD). Moreover, ORR and DCR were 86.84% and 100% (8 CR, 25 PR and 5 SD) based on mRECIST, respectively. 10 pts met the criteria for hepatectomy and 6 pts received liver resection. Among this 6 pts, 5 pts was in stage IIIA and 1 in IIIB before enrollment. No postoperative mortality was observed. Most treatment-related AEs (TRAE) were grade 1-2, and the incidence of grade 3 TRAEs was 14.63%. Grade 3 TRAEs includes decreased platelet count, hypertension, increased ALT, decreased white blood cell count, rash, hematencephalon and upper gastrointestinal hemorrhage.

Conclusions

Systemic therapy using HAIC plus Sintilimab and bev as first-line therapy for initial unresectable HCC was well tolerated and effective. Longer follow up is ongoing.

Clinical trial identification

ChiCTR2000034758.

Legal entity responsible for the study

Shanghai Eastern Hepatobiliary Surgery Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.