LBA2 - Tislelizumab (TIS) versus sorafenib (SOR) in first-line (1L) treatment of unresectable hepatocellular carcinoma (HCC): The RATIONALE-301 Chinese subpopulation analysis

Background

TIS is a humanized monoclonal antibody with high affinity and binding specificity to programmed cell death protein 1 receptor. In the phase 3 trial RATIONALE-301 (NCT03412773), TIS showed non-inferior overall survival (OS) vs SOR (hazard ratio 0.85, 95% confidence interval [CI]: 0.71, 1.02), and was well tolerated in 1L treatment of patients (pts) with unresectable HCC. This analysis assessed and compared efficacy and safety of TIS in the Chinese subgroup with the overall population of RATIONALE-301.

Methods

This open-label trial enrolled systemic therapy-naïve adults with histologically confirmed Barcelona Clinic Liver Cancer Stage C or B HCC. Pts were randomized (1:1) to receive TIS (200 mg IV every 3 weeks [TIS Arm]) or SOR (400 mg orally twice daily [SOR Arm]) until disease progression, intolerable toxicity, or treatment discontinuation due to other reasons. The primary endpoint was OS. Secondary endpoints included objective response rate (ORR), duration of response (DoR), and progression-free survival, all by blinded independent review committee, and safety.

Results

Of 674 randomized pts, 425 were from China. In the Chinese subgroup, median follow-up was 13.8 months (mo, 95%CI: 0.1, 50.8) in TIS arm vs 13.1 mo (95%CI: 0.1, 49.4) in SOR arm, similar to the overall population. Efficacy data in the Chinese subgroup were similar to the overall population and characterised by higher ORR and longer DoR in the TIS arm vs the SOR arm (Table). In the Chinese subgroup, 53 pts (24.9%) had grade ≥3 treatment-related adverse events in TIS arm vs 112 pts (54.6%) in SOR arm, similar to the overall population (22.2% and 53.4%, respectively) Table: LBA2

ITT Analysis Set; Data cutoff: Jul 11, 2022.CI, confidence interval; ITT, intent-to-treat; mo, months; m, median; DoR, duration of response; NE, not evaluable; ORR, confirmed objective response rate; OS, overall survival; PFS, progression-free survival; SOR, sorafenib; TIS, tislelizumab.

Conclusions

TIS demonstrated a numerically longer OS, higher ORR, more durable responses, and a favorable safety profile vs SOR in the Chinese subgroup, consistent with the overall population representing a potential 1L treatment option for Chinese pts with unresectable HCC.

Clinical trial identification

NCT03412773.

Editorial acknowledgement

This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Victoria Dagwell, MSc, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene Ltd.

Funding

BeiGene, Ltd.

Disclosure

K. Hsing-Tao: Other, Personal, Principal Investigator, PI fee: BeiGene Ltd. S. Li: Financial Interests, Personal, Full or part-time Employment: BeiGene, Ltd. Y. Chen: Financial Interests, Personal, Full or part-time Employment: Beigene, Ltd. F. Boisserie: Financial Interests, Personal, Full or part-time Employment: BeiGeneUSA, Inc.; Financial Interests, Personal, Stocks/Shares: BeiGeneUSA, Inc. R. Abdrashitov: Financial Interests, Personal, Full or part-time Employment: BeiGene, Ltd.; Financial Interests, Personal, Stocks/Shares: BeiGene, Ltd. All other authors have declared no conflicts of interest.