1437P - Tislelizumab (TIS) + chemotherapy (CT) vs placebo (PBO) + CT in HER2-negative advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJC): RATIONALE-305 study minimum 3-year survival follow-up

Background

TIS (an anti–programmed cell death protein 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; hazard ratio [HR], 0.80) and pts with PD-L1 Tumour Area Positivity (TAP) score ≥5% (HR, 0.71) in the phase 3 RATIONALE-305 study (NCT03777657). 2-yr OS rates for TIS + CT vs PBO + CT were 32.7% vs 23.4%, respectively. We report efficacy and safety after a minimum 3-yr follow up.

Methods

Adults with locally advanced, nonresectable or metastatic, HER2-negative, untreated GC/GEJC were randomized (1:1) to intravenous TIS 200 mg or PBO every 3 wks + investigator-chosen CT (oxaliplatin + capecitabine or cisplatin + 5-fluorouracil). TAP score was evaluated in tumour tissue using the VENTANA PD-L1 (SP263) assay. Primary endpoint was OS in all randomized pts and pts with PD-L1 TAP ≥5%. Secondary endpoints included investigator-assessed progression-free survival (PFS), objective response rate, duration of response (DoR) per Response Evaluation Criteria In Solid Tumors v1.1, and safety.

Results

A total of 997 pts were randomized (TIS + CT, n=501; PBO + CT, n=496). At 3-yr follow up (min: 36.6 mo), improvements in OS, PFS, and DoR in TIS + CT vs PBO + CT (Table) were maintained. Grade ≥3 treatment-related adverse events (TRAEs) were similar in both arms, occurring in 269/498 pts (54.0%) with TIS + CT and 246/494 pts (49.8%) with PBO + CT; TRAEs led to any treatment discontinuation in 16.7% vs 8.1% and led to death in 1.2% vs 0.4%, respectively.

Conclusions

After a minimum 3-yr follow up, TIS + CT as 1L treatment for GC/GEJC continued to demonstrate clinically meaningful improvements in OS, PFS, and DoR compared with PBO + CT, with no new safety signals. These long-term data further support TIS + CT as a new 1L treatment option for advanced HER2-negative GC/GEJC. Table: 1437P

^aStratified.^bInvestigator evaluated.

Clinical trial identification

NCT03777657.

Editorial acknowledgement

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

Legal entity responsible for the study

BeiGene Co., Ltd.

Funding

BeiGene Co., Ltd.

Disclosure

M. Cruz-Correa: Financial Interests, Personal, Financially compensated role: BeiGene, AbbVie, Genentech, Taiho, Seagen, BMS, Merck, Pfizer, Janssen, Mirati, Tempus, Huyabio, Regeneron, Delfi; Financial Interests, Personal, Proprietary Information: Hopkins University; Financial Interests, Personal, Stocks/Shares: Pan American Center for Oncology Trials University of Puerto Rico Medical Sciences Campus. 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, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Ono Pharmaceuticals, Merck & Co; Financial Interests, Institutional, Local PI: Bayer, AstraZeneca, BeiGene, Taiho, Oncolys Biopharma, Merck Biopharma. 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. K. Lee: Financial Interests, Personal, Advisory Board: AbbVie, Astellas, BMS (Korea), Daiichi Sankyo (Korea), Merck Sharp & Dohme (Korea), MetaFines; Financial Interests, Personal, Invited Speaker: Bayer (Korea), Merck KGaA (Korea); Financial Interests, Institutional, Local PI, For conducting clinical trials: ALX Oncology, Amgen, Arcus Biosciences, Astellas Pharma, AstraZeneca, BeiGene, Bolt Therapeutics, Daiichi Sankyo, Elevar, Erasca, Inc., Exelixis, Genome & Company, GSK, IgM Biosciences, InventisBio, Jazz Pharmaceuticals, Leap Therapeutics, Macrogenics, MedPacto, Medicenna, Merck KGaA, Merck Sharp & Dohme, MetaFines, Ono Pharmaceutical, Panolos Bioscience, Pfizer, Seagen, TRIO Oncology, Taiho Pharmaceutical, Trishula Therapeutics, Wellmarker Bio, Y-Biologics; Non-Financial Interests, Leadership Role, SMC chair of ASPEN-06 study: ALX Oncology. H. Hirano: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Ono Pharmaceutical, Teijin Pharma, Novartis, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Ono Pharmaceutical, Janssen Pharmaceutical, Merck Biopharma, Bristol Myers Squibb, Pfizer, Eisai, Amgen, Astellas, Seagen, MSD, Incyte, BeiGene, Novartis, ALX Oncology, PPD, Nippon Boehringer Ingelheim. D.R. Spigel: Financial Interests, Institutional, Other, Consulting: AstraZeneca, BeiGene, Bristol Myers Squibb, Evidera, GSK, Ipsen Biopharmaceuticals, Janssen, Jazz Pharmaceuticals, Lilly, Molecular Templates, Monte Rosa Therapeutics, Novartis, Pfizer, Regeneron, Sanofi-Aventis, AbbVie, Novocure, Roche/Genentech; Financial Interests, Institutional, Research Grant, Serve as PI: Amgen, Aeglea Biotherapeutics, Agios, Arrys Therapeutics, Astellas, AstraZeneca, Bayer, BeiGene, BIND Therapeutics, Blueprint Medicine, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celldex Therapeutics, Clovis, Daiichi Sankyo, Eisai, Lilly, Genentech/Roche, G1 Therapeutics, Gilead Sciences, GSK, Grail, Hutchinson MediPharma, ImClone Systems, Ipsen, Janssen, Loxo, MacroGenics, MedImmune, Merck, Nektar, Neon Therapeutics, Novartis, Novocure, Rgenix, Seagen, Taiho Oncology, Tarveda, Tizona Therapeutics, Transgene, UT Southwestern, Verastem, Arcus Biosciences, Molecular Template, Cyteir Therapeutics, BioNTech, Apollomics, Pure Tech Health, Elevation Oncology, Repare Therapeutics, Razor Genomics, Denovo Biopharma, Erasca, Kronos Bio, Zai Laboratory, Faeth Therapeutics, Ascendis Pharma, Lyell Immunopharma, Synthekine, Shenzhen Chipscreen Biosciences, AbbVie, AnHeart Therapeutics, Calithera, Endeavor, FujiFilm Pharmaceuticals, Incyte, Jazz Pharmaceuticals, Millennium Pharmaceuticals, Moderna, Monte Rosa Therapeutics, Peloton Therapeutics, Stemline Therapeutics, Tango Therapeutics, Tesaro. L.S. Wyrwicz: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, MSD, Servier, BeiGene, Roche, AstraZeneca; Financial Interests, Personal, Advisory Board: BMS, Servier. R.A. Pazo Cid: Financial Interests, Personal, Speaker, Consultant, Advisor: BeiGene, Roche, Astellas, BMS, Ipsen, Celgene, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Servier, Lilly, BMS; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Ipsen. L. Li: Financial Interests, Personal, Stocks or ownership: BeiGene. T. Sheng: Financial Interests, Personal, Stocks/Shares: BeiGene. S. Yang: Financial Interests, Personal, Stocks or ownership: BeiGene. R. Xu: Financial Interests, Personal, Invited Speaker: BMS, MSD, Hutchison Pharm; Financial Interests, Personal, Advisory Board: Henrui, BeiGene, Astellas, Merck, Junshi, Innovent, Keymed Biosience. M. Moehler: Financial Interests, Personal, Advisory Board: Bayer, Taiho Pharmaceutical, Novartis, MSD, Dragonfly, Astellas, Servier, Amgen, AstraZeneca, BMS, BeiGene, Lilly, Roche, Pfizer, Merck Serono; Financial Interests, Personal, Speaker, Consultant, Advisor: Nordic, Astellas, Daiichi Sankyo, Transcenta, Falk foundation, Sanofi, Pierre Fabre, Servier, AstraZeneca/MedImmune, Bristol Myers Squibb, MSD Oncology, Merck Serono, Roche/Genentech, Amgen. All other authors have declared no conflicts of interest.