70O - Randomized, global, phase III study of tislelizumab (TIS) + chemotherapy (chemo) vs chemo as first-line (1L) therapy for advanced or metastatic esophageal squamous cell carcinoma (ESCC) (RATIONALE-306): Asia subgroup

Background

TIS, an anti-PD-1 antibody, + chemo as 1L therapy demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) vs placebo (PBO) + chemo in patients (pts) with advanced or metastatic ESCC, with a manageable safety profile, at interim analysis of the Phase 3 RATIONALE-306 study. We report data from the Asia subgroup.

Methods

Adults with unresectable locally advanced or metastatic ESCC, with 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, with platinum + fluoropyrimidine, or platinum + paclitaxel until disease progression by INV per RECIST v1.1, intolerable toxicity, or withdrawal. The primary endpoint was OS in the intent-to-treat (ITT) population. Secondary endpoints included: progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR) per INV; and safety.

Results

Of 649 randomized pts, 486 (74.9%) were from Asia (243 pts per arm). At data cutoff (Feb 28, 2022), the median (m) follow-up in the Asia subgroup was 16.5 months (mo) in Arm A vs 10.6 mo in Arm B. OS (mOS 18.3 vs 11.5 mo; unstratified HR 0.67 [95% CI 0.54, 0.84]) and PFS (mPFS 7.2 vs 5.6 mo; unstratified HR 0.62 [95% CI 0.50, 0.76]) were improved in Arm A vs B, respectively. Arm A had higher ORR (64.2% vs 42.8%, odds ratio 2.40 [95% CI 1.66, 3.45]) and longer mDoR (7.1 mo [95% CI 5.6, 8.4] vs 5.6 mo [95% CI 4.4, 7.1]) than Arm B. Similar proportions of pts in Arm A vs B had ≥1 treatment-related AEs (TRAEs; 97.5% vs 98.8%), ≥Grade 3 TRAEs (70.1% vs 68.3%), and TRAEs leading to death (2.1% vs 1.2%), respectively. Serious TRAEs occurred in 29.9% vs 19.8% of pts, and discontinuation due to treatment-emergent AEs occurred in 28.2% vs 18.1%, in Arm A vs B, respectively.

Conclusions

In the Asia subgroup, 1L TIS + chemo demonstrated clinically meaningful improvement in OS and improvements in PFS, ORR, and DoR vs PBO + chemo in pts with advanced or metastatic ESCC, with a manageable safety profile, consistent with published results in the overall population.

Clinical trial identification

NCT03783442.

Editorial acknowledgement

This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Helena Crisford, 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. Kato: Financial Interests, Personal and Institutional, Advisory Board: ONO pharmaceuticals, Bristol Myers Squibb, Merck & Co., Beigene; Financial Interests, Personal and Institutional, Other, Honoraria: ONO pharmaceuticals, Bristol Myers Squibb, Merck & Co.; Financial Interests, Personal and Institutional, Principal Investigator: ONO pharmaceuticals, Bristol Myers Squibb, Merck & Co., Beigene; Financial Interests, Personal and Institutional, Research Grant: ONO pharmaceuticals, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Speaker’s Bureau: ONO pharmaceuticals, Bristol Myers Squibb. H. Yoon: Financial Interests, Personal, Advisory Board: OncXerna, Merck, Zymeworks, MacroGenics, BMS, BeiGene, AstraZeneca; Financial Interests, Personal, Other, Steering committee: Merck, MacroGenics, BeiGene; Financial Interests, Personal, Invited Speaker: BeiGene; Financial Interests, Personal, Research Grant: BeiGene; Financial Interests, Personal, Other, Education symposium: BeiGene; Financial Interests, Personal, Sponsor/Funding: Merck, BMS, MacroGenics, BeiGene, Boston Biomedical, Elevar Therapeutics, CARsgen. R. Hubner: Financial Interests, Personal, Advisory Role: Novartis, Beigene. S.R. Park: Financial Interests, Personal and Institutional, Advisory Board: Genome & Company; Financial Interests, Institutional, Funding: ImmuneOncia. L. Shen: Financial Interests, Institutional, Funding: Jacobio Pharmaceuticals, Baiji Shenzhou (Beijing) Biotechnology Co. Ltd., Yaojie Ankang (Nanjing) Technology Co. Ltd., Beihai Kangcheng (Beijing) Medical Technology, ZaiLab Pharmaceutical (Shanghai), Qilu Pharmaceutical, Beijing Xiantong Biomedical Techno; Financial Interests, Personal, Advisory Role: Mingji biopharmaceutical, Haichuang pharmaceutical, Herbour biomed; Financial Interests, Personal, Speaker’s Bureau: Hutchison Whampoa Hengrui, CSTONE pharmaceutical ZaiLab; Financial Interests, Personal, Advisory Board: MSD, Merk, BMS, BI Sanofi, Roche, Servier. T. Kojima: Financial Interests, Personal and Institutional, Advisory Board: Bristol Myers Squibb, Ono Pharmaceutical Co. Ltd., MSD K.K., OncolysBioPharma Inc., Merck Biopharma Co. Ltd., Astellas Pharma Inc.; Financial Interests, Personal and Institutional, Invited Speaker: OncolysBioPharma Inc.; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb, Ono Pharmaceutical Co. Ltd., MSD K.K., Taiho Pharmaceutical Co. Ltd., Merck Biopharma Co. Ltd.; Financial Interests, Personal and Institutional, Writing Engagements: MSD K.K.; Financial Interests, Institutional, Research Grant: BeiGene Ltd., EPS Corporation, Amgen Inc., Shionogi & Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., Parexel International, Merck Biopharma Co. Ltd. L. Wang: Other, Personal and Institutional, Full or part-time Employment, Employee: BeiGene. Y. Peng: Financial Interests, Personal and Institutional, Full or part-time Employment: BeiGene (Shanghai) Co., Ltd. L. Li: Financial Interests, Personal, Full or part-time Employment: BeiGene (Beijing) Co., Ltd., Beijing, China; Financial Interests, Personal, Stocks/Shares: BeiGene (Beijing) Co., Ltd., Beijing, China; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BeiGene (Beijing) Co., Ltd., Beijing, China; Financial Interests, Personal, Training: BeiGene (Beijing) Co., Ltd., Beijing, China. All other authors have declared no conflicts of interest.