Abstract 178P
Background
Pembrolizumab + chemotherapy significantly improved OS (HR, 0.78; 95% CI, 0.70-0.87; P<0.0001), PFS (HR, 0.76; 95% CI, 0.67-0.85; P<0.0001), and ORR (51.3% vs 42.0%; P=0.00009) vs placebo + chemotherapy in patients with HER2-negative G/GEJ cancer at the protocol-specified interim analysis of KEYNOTE-859 (NCT03675737). Results after an additional 11 months of follow-up are presented.
Methods
Eligible patients had previously untreated locally advanced or metastatic HER2-negative G/GEJ cancer, an ECOG PS of 0 or 1, known PD-L1 combined positive score (CPS), and measurable disease per RECIST v1.1. Patients were randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤35 cycles + investigator’s choice of chemotherapy (5-FU + cisplatin [FP] vs capecitabine + oxaliplatin [CAPOX]). The primary end point was OS; secondary end points included PFS, ORR, and DOR (all per RECIST v1.1 by BICR), and safety.
Results
Median follow-up from randomization to data cutoff (August 22, 2023) was 41.6 months (Q1-Q3, 33.6-48.9). Results were generally consistent between the intention-to-treat (ITT) population and patients with PD-L1 CPS ≥1 and PD-L1 CPS ≥10 (Table). Treatment-related AEs were reported in 751 patients (95.7%; grade 3-5: 466 [59.4%]) for pembrolizumab + chemotherapy and 736 (93.5%; grade 3-5: 404 [51.3%]) for placebo + chemotherapy Table: 178P
| ITT n = 1579 | PD-L1 CPS ≥1 n = 1235 | PD-L1 CPS ≥10 n = 553 | ||||
| Pembro + chemo n = 790 | Pbo + chemo n = 789 | Pembro + chemo n = 618 | Pbo + chemo n = 617 | Pembro + chemo n = 280 | Pbo + chemo n = 273 | |
| OS, median (95% CI), mo | 12.9 (11.9-14.0) | 11.5 (10.6-12.1) | 13.0 (11.6-14.2) | 11.4 (10.5-12.0) | 15.8 (14.0-19.3) | 11.8 (10.3-12.7) |
| HR (95% CI) | 0.79 (0.71-0.88) | 0.75 (0.66-0.85) | 0.64 (0.53-0.78) | |||
| PFS, median (95% CI), mo | 6.9 (6.3-7.2) | 5.6 (5.5-5.7) | 6.9 (6.0-7.2) | 5.6 (5.4-5.7) | 7.8 (6.8-8.5) | 5.6 (5.4-6.7) |
| HR (95% CI) | 0.76 (0.68-0.85) | 0.73 (0.64-0.83) | 0.63 (0.51-0.77) | |||
| ORR, % | 51.0 | 42.0 | 51.8 | 42.6 | 60.0 | 43.2 |
| DOR, median (range), mo | 8.0 (1.2+ to 52.6+) | 5.7 (1.3+ to 44.3+) | 8.3 (1.2+ to 52.6+) | 5.6 (1.3+ to 44.3+) | 10.0 (1.2+ to 52.6+) | 5.7 (1.4+ to 41.0+) |
Conclusions
After a median follow-up of 41.6 months, use of pembrolizumab + chemotherapy continued to show improved clinical outcomes vs placebo + chemotherapy regardless of PD-L1 expression. These results continue to support pembrolizumab + chemotherapy as first-line therapy for patients with locally advanced or metastatic HER2-negative G/GEJ adenocarcinoma. ©2024 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2024 ASCO Annual Meeting. All rights reserved.
Clinical trial identification
NCT03675737.
Editorial acknowledgement
Medical writing assistance was provided by Holly C. Cappelli, PhD, CMPP of ApotheCom (Yardley, PA, USA) and was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
M.H. Ryu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, DAEHWA Pharmaceutical, Daiichi Sankyo, Lilly, MSD, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, DAEHWA Pharmaceutical, Daiichi Sankyo, Lilly, MSD, Novartis, Ono Pharmaceutical, Taiho Pharmaceutical. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: MSD, Daiichi Sankyo; Financial Interests, Personal, Steering Committee Member: Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Indivumed, AstraZeneca; Financial Interests, Personal, Other, Durg supply for clinical trial: Merck; Financial Interests, Institutional, Coordinating PI, Drug supply for clincal trial: MSD; Financial Interests, Institutional, Local PI, drug supply for clinical trial: Zymeworks; Financial Interests, Institutional, Local PI, drug supply for clincial trial: BeiGene; Financial Interests, Personal, Local PI: Roche. L.S. Wyrwicz: Financial Interests, Personal, Advisory Board: BMS, Servier; Financial Interests, Personal and Institutional, Local PI: BMS, MSD, Servier, Beigene, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: AstraZeneca. P.E. Yanez Weber: Financial Interests, Institutional, Other, Honoraria: AstraZeneca, BMS CHILE, MSD, Sanofi/Regeneron; Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb/Medarex, MSD Oncology ; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BMS CHILE. J. Lee: Financial Interests, Personal, Steering Committee Member: Seattle Genetics, AZ; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Daichi Sankyo, Merck MSD, BMS; Non-Financial Interests, Personal, Project Lead: Samsung Bioepis, Genome and Company; Non-Financial Interests, Personal, Advisory Role: Mirati Therapeutics, Trutino Bioscience, Daichi Sankyo; Non-Financial Interests, Personal, Member: KSMO; Non-Financial Interests, Personal, Other, AP Council: ASCO. F. Rivera Herrero: Financial Interests, Personal, Invited Speaker: Roche, MSD, BMS, Servier, Astellas, AMGEN, Merck; Financial Interests, Personal, Advisory Board: MSD, BMS, Servier, Astellas, AMGEN, Astra-Zeneca; Financial Interests, Institutional, Local PI: Astra-Zeneca, MSD, Novartis, SEAGEN, OBT, INSPIRNA. G.V. Alves: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck Serono, MSD Oncology ; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, GSK, Sanofi; Financial Interests, Institutional, Research Funding: AstraZeneca, AVEO, BeiGene, BMS Brazil, Janssen Oncology , MSD Oncology , Roche, Sanofi, Zymeworks; Financial Interests, Institutional, Other, Travel: Jannsen Oncology . M. Garrido: Financial Interests, Personal, Advisory Role: AstraZeneca, MSD, Roche; Financial Interests, Personal, Speaker’s Bureau: Bayer, Bristol Myers Squibb, Merck; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Novartis; Financial Interests, Personal, Other, Travel: Roche. K. Shiu: Financial Interests, Personal, Invited Speaker, Educational Webinars on CRC and UGI cancer management with immunotherapy: BMS; Financial Interests, Personal, Advisory Board, Advisory Board on Regorafenib for chemorefractory mCRC in readiness for NICE application: Bayer; Financial Interests, Personal, Invited Speaker, Educational webinars on Pembrolizumab for MSI-High CRC, as well as OG cancers: MSD; Financial Interests, Personal, Advisory Board, For Pembrolizumab in CRC of OG cancers pre or NICE application or post NICE approval: MSD; Financial Interests, Personal, Invited Speaker, Webinars on updates on management of mCRC: Merck Serono; Financial Interests, Personal, Advisory Board, On Mirati GI Global Advisory Board: Mirati Therapeutics; Financial Interests, Personal, Invited Speaker, To update company on indications/updates in landscape of immunotherapy and vaccines in GI cancers: Nouscom; Financial Interests, Personal, Advisory Board, Advisory on Cancer of Unknown Primary, new indications of molecular profiling using Foundation Medicine 1: Roche; Financial Interests, Personal, Advisory Board, Advisory Board on Lonsurf for chemorefractory mCRC in readiness for NICE application: Servier; Financial Interests, Personal, Advisory Board, For advising on latest trial data on dostarlimab for future trial designs and combinations: GSK; Financial Interests, Personal, Advisory Board, Advising on company IMP for trial expansion/new trial designs, as well as market access in UK: Seagen; Financial Interests, Institutional, Local PI, For MATTERHORN Trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator on KEYNOTE 177, KEYNOTE 859, KEYNOTE 811, LEAP 17, MK1308A-008 trials: MSD; Financial Interests, Institutional, Research Grant, Chief Investigator of investigator initiated, MSD funded NEOPRISM-CRC trial: MSD; Financial Interests, Institutional, Local PI, UCLH PI for LEAP 15 and MK4280A-007 trials: MSD; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for NOUS209-001 trial: Nouscom; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for CUPSICO trial: Roche; Financial Interests, Personal, Steering Committee Member, Steering Committee Member of CUPISCO trial: Roche; Financial Interests, Institutional, Local PI, PI to run BNT 122 trial-01: BioNTech; Non-Financial Interests, Personal, Member: ASCO, Association of Cancer Physicians UK. J. Li: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, HenRui, Lilly O. , MSD, Roche. M.A. Lowery: Financial Interests, Personal, Invited Speaker, Educational session for trainees: Novartis; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: Agios, Servier; Financial Interests, Institutional, Other, Educational Grant: Roche; Financial Interests, Institutional, Research Grant: Genuity Science; Non-Financial Interests, Personal, Principal Investigator: MSD, Basilea, Exelixis, Astellas; Non-Financial Interests, Personal, Principal Investigator, Clinical trial: Daiichi Sankyo, Zymeworks; Non-Financial Interests, Personal, Advisory Role, Speaker: Astellas. F. Cruz: Financial Interests, Personal, Other, Travel: Janssen Oncology , Novartis . 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, Alligator Bioscience AB; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. L. Yin, S. Bordia, P. Bhagia: Financial Interests, Personal, Full or part-time Employment: Merck. All other authors have declared no conflicts of interest.