KEYSTEP-008: phase II trial of pembrolizumab-based combination in MSI-H/dMMR metastatic colorectal cancer

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dc.authorid0000-0003-3550-9993
dc.authorid0000-0002-8530-8420
dc.authorid0000-0002-5103-7095
dc.authorid0000-0001-6188-5664
dc.contributor.authorAndre, Thierry
dc.contributor.authorPietrantonio, Filippo
dc.contributor.authorAvallone, Antonio
dc.contributor.authorGümüş, Mahmut
dc.contributor.authorWyrwicz, Lucjan
dc.contributor.authorKim, Jong Gwang
dc.contributor.authorYalcin, Suayib
dc.date.accessioned2025-05-10T19:35:43Z
dc.date.issued2023
dc.departmentİstanbul Medeniyet Üniversitesi
dc.description.abstractRobust clinical activity has been observed with the immune checkpoint inhibitor pembrolizumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). However, given the response rate of 45% and a median progression-free survival of 16.5 months with first-line pembrolizumab demonstrated in KEYNOTE-177, there is room for improvement. Targeting a second immune receptor, such as CTLA-4, LAG-3, TIGIT, or ILT-4 may improve efficacy of PD-1 inhibition. Here we describe the design and rationale for the open-label, randomized, phase II KEYSTEP-008 trial, which will evaluate the efficacy and safety of pembrolizumab-based combination therapy compared with pembrolizumab monotherapy in chemotherapy-refractory (cohort A) or previously untreated (cohort B) MSI-H/dMMR mCRC.Clinical Trial Registration: NCT04895722 (ClinicalTrials.gov)
dc.description.sponsorshipMerck Sharp Dohme LLC; Bristol-Myers Squibb; Merck Sharp Dohme; BMS; Amgen; Agenus; Incyte; AstraZeneca; Bayer; MSD; Roche; Merck Serono; Eli Lilly; Bristol Myers Squibb; Roche/Genentech
dc.description.sponsorshipThis research is funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. T Andre reports honoraria from Amgen, Aptitude Health, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Pierre Fabre, Roche/Vantana, Sanofi and Servier; consulting or advisory roles for Astellas Pharma, Bristol-Myers Squibb, GamaMabs Pharma, Gilead, GlaxoSmithKline, Gritstone Oncology, Merck Sharp & Dohme, Seagen, and Servier; and Transge3ne Speaker's Bureaus for Bristol-Myers Squibb, Merck Sharp & Dohme, Seagen, and Servier; research funding from Bristol-Myers Squibb and Merck Sharp & Dohme; travel and accommodation expenses from Merck Sharp & Dohme and Bristol-Myers Squibb; and non-remunerated activities for the ARCAD Foundation and GERCOR Group. F Pietrantonio reports honoraria from Servier, Bayer, Astellas, Amgen, Merck-Serono, Pierre-Fabre, MSD, Takeda, and BMS; consulting or advisory roles for Bayer, Merck-Serono, Amgen, MSD, and Organon; research funding from BMS, Amgen, Agenus, Incyte, and AstraZeneca; and travel or accommodation expenses from Merck-Serono and Amgen. A Avallone reports honoraria from Servier, Bayer, Amgen, Pierre-Fabre, Eli Lilly, MSD, AstraZeneca and Eisai; consulting or advisory roles for Amgen, AstraZeneca, MSD, and Servier; research funding from Amgen, Bayer, and BMS; and travel or accommodation expenses from Merck-Serono and Amgen. M Gumus reports honoraria from Amgen, Roche, Abdi Ibrahim, Novartis, and Bayer; consulting or advisory roles for MSD, Bayer, and Gen Drug; speaker bureau for Roche and Amgen; and research funding from Amgen. L Wyrwicz reports research funding from Merck Sharp & Dohme. S Yalcin reports honoraria from Amgen, Roche, Abdi Ibrahim, Novartis, Bayer, Gen Ilac, Eli Lilly, Merck Serono, and Eczacibasi; consulting or advisory roles for MSD, Roche, Bayer, Gen Drug, Amgen, and Eli Lilly; speaker bureau for Roche, Amgen, Merck, Eli Lilly, Nobel, and Roche; stock interests in Curis; and travel or accommodation expenses from Gen Ilac and AstraZeneca. MK reports research funding from MSD, AstraZeneca, Roche, and BMS. S Lonardi reports consulting or advisory roles for Amgen, Merck Serono, Eli Lilly, AstraZeneca, Incyte, Daiichi-Sankyo, Bristol Myers Squibb, Servier, Merck Sharp & Dohme; speaker bureau for Roche, Eli Lilly, Briston Myers Squibb, Servier, Merck Serono, Pierre Fabre, GlaxoSmithKline, Amgen, and AstraZeneca; and research funding from Amgen, Merck Serono, Bayer, Roche, Eli Lilly, AstraZeneca, and Bristol Myers Squibb. J Zolnierek reports honoraria and a consulting or advisory role for Merck. A Odeleye-Ajakaye and P Leconte report employment and stock interests at Merck Sharp & Dohme. D Fogelman reports employment at Merck Sharp & Dohme. TW Kim reports research funding from Roche/Genentech. JG Kim has no conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Medical writing and editorial assistance were provided by M Aggarwal and HC Cappelli of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
dc.identifier.doi10.2217/fon-2022-1105
dc.identifier.endpage2452
dc.identifier.issn1479-6694
dc.identifier.issn1744-8301
dc.identifier.issue37
dc.identifier.pmid37701986
dc.identifier.scopusqualityQ2
dc.identifier.startpage2445
dc.identifier.urihttps://doi.org/10.2217/fon-2022-1105
dc.identifier.urihttps://hdl.handle.net/20.500.14730/8949
dc.identifier.volume19
dc.identifier.wosWOS:001064782800001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherTaylor & Francis Ltd
dc.relation.ispartofFuture Oncology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250302
dc.subjectfavezelimab
dc.subjectMK-4830
dc.subjectMSI-H/dMMR colorectal cancer
dc.subjectpembrolizumab
dc.subjectquavonlimab
dc.subjectvibostolimab
dc.titleKEYSTEP-008: phase II trial of pembrolizumab-based combination in MSI-H/dMMR metastatic colorectal cancer
dc.typeArticle

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