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dc.contributor.authorHamilton, E. P.
dc.contributor.authorWang, J. S.
dc.contributor.authorPluard, T. J.
dc.contributor.authorJohnston, S. R. D.
dc.contributor.authorMorikawa, A.
dc.contributor.authorDees, E. C.
dc.contributor.authorJones, R. H.
dc.contributor.authorHaley, B. B.
dc.contributor.authorArmstrong, Anne C
dc.contributor.authorCohen, A. L.
dc.contributor.authorMunster, P. N.
dc.contributor.authorWright, G. L. S.
dc.contributor.authorKayali, F.
dc.contributor.authorKorpal, M.
dc.contributor.authorXiao, J. J. A.
dc.contributor.authorLong, J.
dc.contributor.authorDestenaves, B.
dc.contributor.authorGao, L.
dc.contributor.authorGualberto, A.
dc.contributor.authorJuric, D.
dc.date.accessioned2022-01-11T11:59:52Z
dc.date.available2022-01-11T11:59:52Z
dc.date.issued2021en
dc.identifier.citationHamilton EP, Wang JS, Pluard TJ, Johnston SRD, Morikawa A, Dees EC, et al. Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Vol. 39, Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 1018–1018.en
dc.identifier.doi10.1200/JCO.2021.39.15_suppl.1018en
dc.identifier.urihttp://hdl.handle.net/10541/624895
dc.description.abstractBackground: H3B-6545, a selective, small molecule covalent antagonist of ERα demonstrated preclinical and preliminary clinical activity against ER+ breast cancer (Hamilton EP, SABCS, 2020). This study evaluated the activity and tolerability of H3B-6545 in patients (pts) with metastatic ER+, HER2-, breast cancer refractory to endocrine therapy. Methods: Patients received H3B-6545 once daily at the recommended phase II dose of 450 mg. The primary objective of the phase II is to estimate the objective response rate (ORR), progression-free survival (PFS), clinical benefit rate (CBR) and secondary objectives include safety. Results: 83 pts were treated with 450 mg in the phase II part of the trial. Additionally, 11 pts were treated with 450 mg in the phase I part of the trial and are included in this analysis. Median age was 62 years (range: 38 to 87 years), 81% had liver and/or lung metastases, and the median number of prior therapies for metastatic disease was 3 (range: 1 to 8). Prior CDK4/6 inhibitors, aromatase inhibitors, fulvestrant, and chemotherapy were received by 85%, 80%, 72%, and 50% of the pts, respectively. 58 pts (62%) had detectable ESR1 mutations in liquid biopsies, including 10 (11%) and 19 pts (20%) who had clonal Y537S and clonal D538G mutation, respectively. As of January 29, 2021, grade (gr) 2 or higher adverse events (AE) reported in ≥10% were anemia (19%), fatigue (16%), nausea (17%), and diarrhea (12%). Laboratory gr 2 or higher abnormalities reported in ≥10% pts were creatinine clearance decrease (38%), hemoglobin decrease (37%), bilirubin increase (12%), ALT increase (14%), AST increase (13%), and creatinine increase (11%). AE of gr 1 sinus bradycardia (asymptomatic) was reported in 34% and gr 2 (symptomatic, no intervention needed) was reported in 5%. Gr 2 and 3 QTcF prolongation were reported in 2 and 3 pts, respectively. There were no treatment-related deaths. Efficacy estimates are presented in the table below. Responses were observed in heavily pretreated pts, pts with visceral metastases and in pts who received prior fulvestrant, CDK4/6 inhibitor, and/or chemotherapy in the metastatic setting. Conclusions: H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients. Clinical activity was observed in pts with ESR1 mutations.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1200/JCO.2021.39.15_suppl.1018en
dc.titlePhase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER plus ), human epidermal growth factor receptor 2 negative (HER2-) advanced breast canceren
dc.typeMeetings and Proceedingsen
dc.contributor.departmentSarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TNen
dc.identifier.journalJournal of Clinical Oncologyen
dc.description.noteen]


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