BeiGene shared updates from its solid tumor development program for cornerstone PD-1 antibody tislelizumab at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris. Results from the Phase 3 RATIONALE 301 trial of tislelizumab versus sorafenib as first-line treatment in patients with unresectable hepatocellular carcinoma were accepted as a late-breaking abstract (LBA36) and presented at an oral session on Saturday, September 10. In the final analysis of 674 patients enrolled from Asia, Europe, and U.S., RATIONALE 301 met its primary endpoint of overall survival (OS) non-inferiority, with a median OS of 15.9 months for tislelizumab compared with an OS of 14.1 months for sorafenib (HR: 0.85 [95.003% CI: 0.712, 1.019]); superiority was subsequently tested, which was not met.

OS data were consistent across all pre-specified subgroups, including regions. In the RATIONALE 301 trial, tislelizumab was associated with a higher objective response rate (ORR) (14.3% vs. 5.4%) and more durable responses (median duration of response (DoR) 36.1 months vs.

11.0 months) compared with sorafenib. Median progression-free survival (PFS) for tislelizumab versus sorafenib was 2.1 months vs. 3.4 months respectively; HR: 1.11 [95% CI: 0.92, 1.33].

The safety profiles for tislelizumab and sorafenib treatments were consistent with previous studies, and tislelizumab demonstrated a comparatively favorable profile versus sorafenib with lower incidence rates of grade >3 adverse events (AEs) and AEs leading to discontinuation (48.2% vs 65.4% and 10.9% vs 18.5% respectively). AEs leading to death were low across both tislelizumab (4.4%) and sorafenib (5.2%) arm.