BeiGene (NASDAQ: BGNE, HKG: 6160, SHA: 688235) presented the latest results of the global Phase III RATIONALE 301 study evaluating tislelizumab in first-line unresectable hepatocellular carcinoma (HCC) at the 2022 European Society for Medical Oncology (ESMO) meeting. The study, which enrolled 674 patients in the US, Europe, and Asia, met its primary endpoint, demonstrating that tislelizumab was non-inferior to sorafenib in terms of overall survival (OS).
Study Design and Results
The randomized RATIONALE 301 study compared the efficacy of tislelizumab with sorafenib in first-line unresectable HCC. The primary endpoint was the non-inferiority comparison of OS between the two treatment groups. Key secondary endpoints included the overall response rate (ORR) assessed by the blinded independent review committee (BIRC), as well as efficacy assessment, health-related quality of life measures, and safety and tolerability.
Results showed that median OS was 15.9 months with tislelizumab versus 14.1 months with sorafenib (HR: 0.85 [95.003% CI: 0.712, 1.019]). The trial did not yield superiority data, but OS data showed consistency across all prespecified subgroups, including regions. For secondary endpoints, tislelizumab had a higher ORR (14.3% vs 5.4%) and a more durable response (median duration of response [DoR]: 36.1 months vs 11.0 months). Median progression-free survival (PFS) was 2.1 months in the tislelizumab group and 3.4 months in the sorafenib group.
Safety Profile
The safety profile of tislelizumab was consistent with previous studies, showing a relatively favorable safety profile compared to sorafenib. The incidence of grade ≥ 3 adverse events (AEs) was lower with tislelizumab (48.2% vs 65.4%), as was the rate of AEs leading to discontinuation (10.9% vs 18.5%). AEs leading to death were lower in both the tislelizumab group (4.4%) and the sorafenib group (5.2%).
Current Status of Tislelizumab
Tislelizumab has 9 approved indications in China, with the 10th and 11th indications currently under review. These include its use in combination with chemotherapy as a first-line treatment for advanced or metastatic gastric or gastroesophageal junction (GC/GEJ) adenocarcinoma with tumors expressing PD-L1, and as a first-line monotherapy in unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC).-Fineline Info & Tech
