Inhibition of lysine acetyltransferase KAT6 in ER+HER2− metastatic breast cancer: a phase 1 trial
Mukohara T, Park Y, Sommerhalder D, Yonemori K, Hamilton E, Kim S, Kim J, Iwata H, Yamashita T, Layman R, Mita M, Clay T, Chae Y, Oakman C, Yan F, Kim G, Im S, Lindeman G, Rugo H, Liyanage M, Saul M, Le Corre C, Skoura A, Liu L, Li M, LoRusso P. Inhibition of lysine acetyltransferase KAT6 in ER+HER2− metastatic breast cancer: a phase 1 trial. Nature Medicine 2024, 30: 2242-2250. PMID: 38824244, PMCID: PMC11333285, DOI: 10.1038/s41591-024-03060-0.Peer-Reviewed Original ResearchConceptsProgression-free survivalAntitumor activityEpidermal growth factor receptor-negativeBreast cancer preclinical modelsMedian progression-free survivalPhase 1 dose-escalationTreatment-related adverse eventsDose-expansion studyEstrogen receptor-positiveMetastatic breast cancerPhase 1 trialFirst-in-humanFulvestrant combinationReceptor-negativeReceptor-positiveEvaluation of antitumor activitySecondary endpointsPreclinical modelsSafety profileAdverse eventsBreast cancerApproximately doseClinical proofMonotherapyResponse rateA phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer.
Mukohara T, Park Y, Sommerhalder D, Yonemori K, Kim S, Kim J, Iwata H, Yamashita T, Layman R, Kim G, Im S, Lindeman G, Rugo H, Liyanage M, Homji Mishra N, Maity A, Bogg O, Liu L, Li M, LoRusso P. A phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer. Journal Of Clinical Oncology 2024, 42: 3006-3006. DOI: 10.1200/jco.2024.42.16_suppl.3006.Peer-Reviewed Original ResearchHER2- metastatic breast cancerTreatment-related adverse eventsMetastatic breast cancerCirculating tumor DNABreast cancerGene mutationsFrequent treatment-related adverse eventsMedian duration of follow-upAntitumor activityDuration of follow-upClinical benefit rateProgression-free survivalHER2 breast cancerMutant allele frequencyExpansion doseFulvestrant combinationMedian DoRESR1 mutationsMetastatic settingDose modificationEndocrine therapySystemic therapyMedian durationTumor DNACDK4/6 inhibitors
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