Study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in combination with fulvestrant in patients with advanced hormone receptor positive HER2 negative breast cancer (HR plus BC)
AuthorsHowell, Sacha J
Krebs, Matthew G
Arkenau, H. T.
Mansi, J. L.
Gradishar, W. J.
Coombes, R. C.
AffiliationDivision Of Cancer Sciences, The University of Manchester, Manchester, UK
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AbstractBackground CDK7 inhibition is a promising therapeutic strategy in cancer; acting as a regulator of transcription, the cell cycle and endocrine receptor signalling. Patients with HR+BC post CDK4/6 inhibitor treatment have a poor prognosis; median progression free survival (mPFS) of ? 8 weeks for fulvestrant post CDK4/6i in HR+BC [1,2]. Pre-clinical HR+BC models indicate the potential for synergy when the CDK7 inhibitor samuraciclib is combined with fulvestrant . Methods This single arm cohort assessed the tolerability and efficacy of samuraciclib in combination with fulvestrant in patients with advanced HR+BC; all patients had previously received an aromatase inhibitor and a CDK4/6 inhibitor for advanced disease. Results 31 patients with HR+BC received the combination of standard dose with fulvestrant and samuraciclib. 6 patients received samuraciclib dose of 240mg once daily (OD) and 25 patients a dose of 360mg (OD). The combination treatment was generally well tolerated, with adverse drug reactions (AE) of note being G1-2 nausea, vomiting and diarrhoea; the majority of patients staying on treatment until disease progression. RECIST evaluation indicates evidence of reduction in tumor disease burden, including a partial response in one patient who has been on treatment for ? 1 year. Graphic illustrations of data, including �waterfall� and �swimmer� plots, will be presented. Conclusions Samuraciclib has demonstrated an acceptable safety profile with evidence of anti-tumour activity in combination with fulvestrant for patients with advanced HR+BC who have progressed on their prior CDK4/6i.
CitationHowell SJ, Krebs MG, Lord S, Kenny L, Bahl A, Clack G, et al. 265P Study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in combination with fulvestrant in patients with advanced hormone receptor positive HER2 negative breast cancer (HR+BC). Vol. 32, Annals of Oncology. Elsevier BV; 2021. p. S477�8.
JournalAnnals of Oncology