LBA2 Sintilimab plus bevacizumab biosimilar vs sorafenib as first-line treatment for advanced hepatocellular carcinoma (ORIENT-32)2

Abstract

ORIENT-32 is a randomized, open-label, multi-center phase II/III study to evaluate the efficacy and safety of sintilimab (anti-PD-1 antibody) plus a bevacizumab biosimilar (anti-VEGF antibody), versus sorafenib as first-line treatment for advanced hepatocellular carcinoma (HCC). The phase II part has demonstrated an acceptable safety of this combination. Here we report the result of phase III part (NCT03794440). Patients (pts) with unresectable or metastatic, systemic treatment naive HCC were enrolled and randomized (2:1) to receive sintilimab (200 mg IV Q3W) plus bevacizumab biosimilar (15 mg/kg IV Q3W) (SinBev arm) or sorafenib (400 mg orally, BID) (Sor arm). Stratification factors were macrovascular invasion and/or extrahepatic metastasis (presence vs absence), baseline alpha fetoprotein level (< 400 vs ≥400 ng/mL) and ECOG PS (0 vs 1). The primary endpoints were OS and PFS by independent radiographic review committee (IRRC) per RECIST 1.1. As data cutoff date (Aug 15, 2020), 571 pts were enrolled to SinBev arm (n=380) and Sor arm (n=191). The baseline characteristics were well balanced between two arms, with most pts had hepatitis B infection (94.2%) and 4.2% of pts with Child-Pugh B. With a median follow-up of 10.0 m, median OS was significantly longer in SinBev arm than that in Sor arm (NE vs. 10.4 m, HR 0.57, 95%CI: 0.43-0.75, P<0.0001). Median PFS was significantly improved in SinBev arm as compared with Sor arm (4.5 m vs. 2.8 m, HR 0.57, 95%CI: 0.46-0.70, P<0.0001). The superior OS and PFS benefits with SinVev over Sor were generally consistent across all relevant subgroups. Among pts with evaluable tumor assessment at baseline, the confirmed ORR by IRRC per RECIST 1.1 was 20.3% (74/364, 95%CI: 16.3%-24.8%) in SinBev arm and 4.1% (7/172, 95%CI: 1.7%-8.2%) in Sor arm. Of pts receiving at least one drug dose, the incidences of treatment related adverse events were 88.7% in SinBev arm (n=380) and 93.5% in Sor arm (n=185). Grade 3-4 TRAEs occurred in 33.7% and 35.7% of pts, respectively. Sintilimab plus bevacizumab biosimilar as first-line treatment was associated with significantly improved clinical benefits than sorafenib in pts with advanced HCC.