1514P - Randomized, global, phase III study of tislelizumab (TIS) + chemotherapy (chemo) vs placebo (PBO) + chemo as first-line (1L) treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC): RATIONALE-306 update

Background

At interim analysis (IA) of RATIONALE-306 (NCT03783442), 1L TIS + chemo demonstrated a statistically significant, clinically meaningful improvement in overall survival (OS) vs PBO + chemo, with a manageable safety profile, in patients (pts) with advanced/metastatic ESCC. Here, we report updated efficacy and safety data with minimum (min) 2 years’ follow-up.

Methods

Adults with unresectable locally advanced recurrent/metastatic ESCC and no prior systemic treatment for advanced disease were enrolled and randomized (1:1; stratified by region, prior definitive therapy, and investigator [INV]-chosen chemo) to receive TIS 200 mg (Arm A) or PBO (Arm B) IV Q3W + chemo (platinum + fluoropyrimidine or platinum + paclitaxel), until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS in the intent-to-treat population. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) per INV, and safety.

Results

649 pts were randomized (Arm A n=326, Arm B n=323). At data cutoff (Dec 31, 2022), min study follow-up was 25.2 months; improvements in OS, PFS, ORR, and DoR in Arm A vs B (Table) were maintained relative to the IA. Similar to the IA, incidences of any-grade (96.6% vs 96.3%) or ≥grade 3 (66.7% vs 64.5%) treatment-related adverse events (TRAEs) were comparable between Arms A and B, respectively; treatment-emergent adverse events leading to treatment discontinuation were higher in Arm A (31.8%) vs B (22.1%). In Arm A vs B, respectively, serious TRAEs occurred in 29.3% vs 19.6% of pts; TRAEs leading to death occurred in 1.9% and 1.2%.

Table: 1514P

Conclusions

After min 2 years’ follow-up, 1L TIS + chemo continued to demonstrate clinically meaningful improvements in OS and PFS and durable tumour response benefit vs PBO + chemo in pts with advanced/metastatic ESCC, with no new safety signals.

Clinical trial identification

NCT03783442.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Adeline Lum Nde, PhD, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

R. Hubner: Financial Interests, Invited Speaker: Eisai; Financial Interests, Advisory Board: BeiGene; Financial Interests, Advisory Role: Novartis, Ipsen. K. Kato: Financial Interests, Speaker’s Bureau: Ono, BMS, MSD; Financial Interests, Research Grant: ONO; Financial Interests, Principal Investigator: BMS, Ono, MSD, Bayer, BeiGene, AstraZeneca; Financial Interests, Advisory Role: BMS, Ono, MSD, Bayer, BeiGene, AstraZeneca, Seagen, Servier. T. Kojima: Financial Interests, Invited Speaker: MSD, Bristol Myers Squibb, Ono Pharmaceutical; Financial Interests, Advisory Board: Boehringer Ingelheim, Kyowa Kirin, Taiho Pharmaceutical; Financial Interests, Research Grant: AstraZeneca, BeiGene, MSD, Amgen, Chugai Pharmaceutical, Taiho Pharmaceutical, Shionogi Pharma, Amgen Astellas BioPharma. L.S. Wyrwicz: Financial Interests, Personal, Advisory Board: BMS, Servier; Financial Interests, Personal and Institutional, Invited Speaker: BMS, MSD, Servier, BeiGene, Roche, AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca. H. Wu: Financial Interests, Full or part-time Employment: BeiGene; Financial Interests, Stocks/Shares: BeiGene. Y. Peng: Financial Interests, Full or part-time Employment: BeiGene. L. Wang: Other, Full or part-time Employment, Full time employment: BeiGene. L. Li: Financial Interests, Full or part-time Employment: BeiGene; Financial Interests, Stocks/Shares: BeiGene; Financial Interests, Training: BeiGene. H.H. Yoon: Financial Interests, Institutional, Invited Speaker: BeiGene; Non-Financial Interests, Writing Engagement: BeiGene; Financial Interests, Personal, Expert Testimony: MJH Life Sciences; Financial Interests, Institutional, Advisory Board: ALX Oncology, AstraZeneca, BeiGene, Bristol Myers Squibb, Macrogenics, Merck, OncXerna, Zymeworks, Novartis, Astellas, Amgen, Elevation Oncology; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, CARsgen Therapeutics, Merck, BeiGene; Financial Interests, Institutional, Other, Support for travel: BeiGene. All other authors have declared no conflicts of interest.