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)

Abstract

Background 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 [3]. 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.