397MO - Tislelizumab (TIS) plus chemotherapy (CT) vs placebo (PBO) plus CT in HER2-negative advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma (GC/GEJC): PD-L1 biomarker analysis from RATIONALE-305

Background

TIS (an anti–PD-1 antibody) + CT demonstrated significant overall survival (OS) benefit vs PBO + CT as first-line (1L) therapy for advanced GC/GEJC in all randomized patients (pts; HR=0.80) and pts with PD-L1 Tumor Area Positivity (TAP) score ≥5% (HR=0.71) (phase 3 RATIONALE-305 study, NCT03777657). Here we report exploratory analyses of OS subgroup results by PD-L1 expression status and concordance between PD-L1 TAP score and combined positive score (CPS).

Methods

Adults with GC/GEJC were randomized (1:1) to IV TIS 200 mg or PBO every 3 weeks + investigator-chosen CT (oxaliplatin + capecitabine or cisplatin + 5-fluorouracil). The primary endpoint was OS in all randomized pts and in pts with PD-L1 TAP ≥5%. Tissue samples were stained using the VENTANA PD-L1 (SP263) assay. PD-L1 expression was prospectively assessed by TAP and rescored post hoc by CPS. OS with exploratory PD-L1 score cutoffs (TAP: 1%, 10%; CPS: 1, 5, 10), concordance between TAP and CPS at multiple cutoffs, and interclass correlation coefficient (ICC) were investigated.

Results

Of 997 pts randomized (TIS + CT, n=501; PBO + CT, n=496), 281/28.2% and 885/88.8% had baseline PD-L1 TAP ≥10% and ≥1%, respectively. At final analysis (min follow-up: 24.6 mo), OS improvement with TIS + CT vs PBO + CT was observed in subgroups of PD-L1 TAP score ≥10% and ≥1% (Table). ICC between TAP and CPS was 0.81 (95% CI 0.79–0.83). TAP and CPS scores showed substantial concordance in terms of overall percentage agreement and Cohen’s Kappa (N=974). Table: 397MO

Conclusions

The addition of TIS to CT as 1L treatment for GC/GEJC improved OS in pts with PD-L1 TAP ≥10% and ≥1%. These data, with prior data from pts with PD-L1 TAP ≥5% and all randomized pts, support TIS + CT as a new 1L treatment option for advanced HER2-negative GC/GEJC. Concordant TAP and CPS results suggest both methods are viable for clinical PD-L1 expression measurement in pts with GC/GEJC.

Clinical trial identification

NCT03777657.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Melanie Meister-Broekema, PhD, of Parexel, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

M. Moehler: Financial Interests, Personal, Advisory Board: BMS, Servier, Amgen, Lilly, BeiGene, Novartis, Taiho, Daiichi Sankyo, Amgen, MD; Financial Interests, Personal, Invited Speaker: MSD, BMS, Falk foundation, AIO, BeiGene, Amgen; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Expert Testimony: Sanofi; Financial Interests, Personal, Other, Chair: EORTC. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, Iqvia, MSD, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. K. Kato: Financial Interests, Personal, Invited Speaker: ONO Pharmaceutical, Bristol Myers Squibb, Merck and Co; Financial Interests, Personal, Advisory Board: ONO Pharmaceutical, Bristol Myers Squibb, Merck and Co, Bayer, AstraZeneca, BeiGene, Taiho, Merck Biopharma, Amgen, Novartis; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: ONO Pharmaceuticals, Merck & Co, Bayer, AstraZeneca, BeiGene, Chugai, Taiho, Oncolys Biopharma, Janssen Pharmaceutical. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Genentech Inc., Ikena Oncology, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc., Scorpion Therapeutics, Tolremo Therapeutics, CARSgen Therapeutics, hC Bioscience Inc., Takeda Pharmaceuticals International AG, Alentis Therapeutics, Immodulon Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex/HMP; Financial Interests, Personal, Advisory Board: Cardiff Oncology, Aveo Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeutics, 1TRIALSP, Alentis Therapeutics, Pangaea Oncology; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., Janssen-Cilag International NV, Merck Health KGaA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc., BeiGene, Boehringer Ingelheim, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer - AECC; Non-Financial Interests, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA - Clinical Hospital of Valencia, IdiSNA - Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer - EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGaA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. M. Cruz-Correa: Financial Interests, Institutional, Research Grant: Merck, Seagen, BMS, Taiho, Pfizer, Janssen, AbbVie, Genentech, Incyte, Huyabio, BeiGene. L.S. Wyrwicz: Financial Interests, Invited Speaker: BMS, MSD, Servier, BeiGene, Roche, AstraZeneca; Financial Interests, Advisory Role: BMS, Servier. 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. L. Evesque: Financial Interests, Personal, Advisory Board: Servier, Amgen, MSD, Merck, Astellas. L. Fornaro: Financial Interests, Advisory Board: MSD, BMS, Amgen; Financial Interests, Invited Speaker: MSD, BMS, Servier. L. Li, T. Sheng, H. Hu: Financial Interests, Full or part-time Employment: BeiGene. All other authors have declared no conflicts of interest.