Toripalimab plus bevacizumab as first-line treatment for advanced hepatocellular carcinoma: A single-arm phase II study.

435 Background: Anti-PD-1/PD-L1 combining with antiangiogenic agents has showed encouraging anti-tumor efficacy for treating advanced hepatocellular carcinoma (HCC). Toripalimab, a humanized monoclonal antibody against PD-1, has already been approved for melanoma, nasopharyngeal carcinoma and urothelial carcinoma in China. Therefore, we aimed to assess the safety and efficacy of toripalimab plus bevacizumab as a first-line treatment for unresectable HCC. Methods: This is a multicenter, single-arm, open-label, phase II study. Patients with unresectable locally advanced or metastatic HCC, BCLC stage C or B, Child-Pugh stage A, ECOG PS ≤ 1, at least one measurable lesion, no prior systemic therapy, were enrolled and treated with toripalimab (240mg, IV, D1) plus bevacizumab (15 mg/kg, IV, D1) every 3 weeks as first-line treatment until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoints were tolerability and objective response rate (ORR, per RECIST 1.1 by investigators). The secondary endpoints included the ORR (per mRECIST by independent review committee), the disease control rate (DCR) and progressive free survival (PFS), DoR, time-to-progression (TTP), time-to-response (TTR) and OS. Tumor response was assessed every 6 weeks. Results: As the data cut-off dateofJune 23, 2021,54 pts were enrolled (males 48; median age 54 years [range 26-68]; ECOG PS 0-1; 87.0% with HBV infection; 74.1% in BCLC stage C; 74.1% had received previous local treatment). All pts received at least one cycle of toripalimab plus bevacizumab treatment with median cycles 10 [range 1-18]. Among 52 evaluable patients, per RECIST v1.1, ORR was 32.7% (17/52) with 1 CR and 16 PR, and DCR was 78.8% (41/52); per mRECIST, ORR was 46.2% (95% CI: 32.2-60.5%) and DCR was 94.2% (95% CI: 84.1-98.8%). The median PFS was 9.9 months (95%CI: 5.5-11.0) and median OS has not reached. Most treatment related adverse events (TRAEs) were grade 1-2. Grade ≥3 TRAEs occurred in 25.9% pts, SAEs occurred in 27.8% pts, and grade ≥3 irAEs occurred in 11.1% pts. No treatment-emergent adverse event (TEAE) leading to death occurred in the study. Conclusions: Toripalimab in combination with bevacizumab as first-line treatment showed promising antitumor activity in patients with advanced HCC, and a manageable safety profile. A randomized phase 3 trial of toripalimab plus bevacizumab versus sorafenib (NCT04723004) are ongoing to further validate the efficacy of combination as first-line treatment in advanced HCC patients. Clinical trial information: NCT04605796.