395MO - Tislelizumab (TIS) + chemotherapy (CT) vs placebo (PBO) + CT in advanced or metastatic esophageal squamous cell carcinoma (ESCC): PD-L1 biomarker analysis from RATIONALE-306

Background

TIS (an anti–PD-1 antibody) + CT demonstrated significant overall survival (OS) benefit vs PBO + CT as first-line (1L) therapy for advanced ESCC in all randomized patients (pts; stratified HR 0.66) and pts with PD-L1 Tumor Area Positivity (TAP) score ≥10% (stratified HR 0.62) (RATIONALE-306; NCT03783442). Sustained survival benefit was observed at 3 yrs follow-up. Here we report exploratory analyses of OS by PD-L1 expression status and concordance of PD-L1 TAP and combined positive score (CPS).

Methods

Adults with advanced ESCC were randomized (1:1) to IV TIS 200 mg or PBO every 3 wks + investigator-chosen CT (platinum + fluoropyrimidine or platinum + paclitaxel) until disease progression or intolerable toxicity. The primary endpoint was OS. Tissue samples were stained using the VENTANA PD-L1 (SP263) assay. PD-L1 expression was assessed by TAP and rescored post hoc by CPS. OS with different PD-L1 cutoffs, concordance between TAP and CPS at multiple cutoffs, interclass correlation coefficient (ICC), and Cohen’s Kappa were investigated.

Results

Among 649 randomized pts, PD-L1 status was evaluable in 542 for TAP and 537 for CPS. 223/34%, 135/21%, 123/19% and 61/9% of pts had PD-L1 TAP score ≥10%, 5 to <10%, 1 to <5% and <1%, respectively. After a minimum 3-yr follow-up, OS improvement with TIS + CT vs PBO + CT was seen in PD-L1 subgroups with TAP score ≥1%, while small subgroup size with TAP score <1% limited interpretation (Table). OS results defined by TAP and CPS were similar. ICC between TAP and CPS was 0.85 (95% CI 0.80–0.88). TAP and CPS scores showed substantial concordance in overall percentage agreement and Cohen’s Kappa.

Conclusions

Exploratory PD-L1 subgroup results with prior results from all randomized pts, support TIS + CT as a new 1L treatment option for pts with advanced ESCC. The concordance of TAP and CPS scoring methods indicate that both are viable clinical measurements of PD-L1 expression in pts with ESCC. Table: 395MO

Clinical trial identification

NCT03783442.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Lauren D. Van Wassenhove, PhD, of Parexel, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

K. Kato: Financial Interests, Institutional, Expert Testimony: ONO; Financial Interests, Advisory Role: Bristol Myers Squibb, BeiGene/ Novartis, AstraZeneca, Roche, Bayer, Merck & Co., Merck Bio, Janssen, Chugai. R. Hubner: Financial Interests, Invited Speaker: Eisai; Financial Interests, Advisory Board: Novartis, Ipsen, BeiGene. S.R. Park: Financial Interests, Research Grant: ImmuneOncia, Incyte, Ono Pharma Korea Co; Financial Interests, Advisory Role: BeiGene, Pfizer; Financial Interests, Invited Speaker: MSD. T. Kojima: Financial Interests, Personal, Invited Speaker: MSD, Bristol Myers Squibb, Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Kyowa Kirin, Taiho Pharmaceutical; Financial Interests, Institutional, Invited Speaker: AstraZeneca, BeiGene, MSD, Amgen, Chugai Pharmaceutical, Taiho Pharmaceutical, Shionogi Pharma, Amgen Astellas BioPharma. L.S. Wyrwicz: Financial Interests, Invited Speaker: BMS, MSD, Servier, BeiGene, Roche, AZ; Financial Interests, Advisory Role: BMS, Servier. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Pierre Fabre, BMS, Bayer; Non-Financial Interests, Member of Board of Directors: Federation Francophone de Cancerologie Digestive. K. Geboes: Financial Interests, Institutional, Advisory Board: BMS, MSD, Ipsen, Servier. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, Agenus, ALX, Arcus Biosciences, Astellas, AstraZeneca, Bayer, BeiGene, BioNTech, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Debiopharm, Elmedix, Eisai, GSK, Hoopika Biotech, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Seattle Genetics, Servier, Simcere, Takeda, Taiho, Terumo; Financial Interests, Personal, Invited Speaker: Amgen, Pfizer. R.A. Pazo Cid: Financial Interests, Personal, Advisory Board: Roche, BMS, Servier, Ipsen; Financial Interests, Personal, Invited Speaker: Servier, BMS, Roche, Eisai; Financial Interests, Personal, Expert Testimony: Lilly, AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, Support for manuscript presentation (funding, provision of study materials, medical writing, article processing charges): Ipsen, Astellas. H. Wu: Financial Interests, Stocks/Shares: BeiGene; Financial Interests, Full or part-time Employment: BeiGene. J. Shi, S. Yan: Financial Interests, Full or part-time Employment: BeiGene. L. Li: Financial Interests, Full or part-time Employment: BeiGene; Financial Interests, Stocks/Shares: BeiGene. H. Yoon: Financial Interests, Advisory Role: BeiGene, ALX Oncology, BMS, Macrogenics, Merck, OncXerna, Zymeworks, Novartis, Astellas, Amgen, Elevation Oncology; Financial Interests, Expert Testimony: MJH Life Sciences; Financial Interests, Research Grant: CARsgen, Merck, Bristol Myer Squibb, BeiGene; Financial Interests, Invited Speaker: BeiGene. All other authors have declared no conflicts of interest.