Abstract GS3-10: 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)

Background: CDK7 inhibition is a promising therapeutic strategy in cancer; acting as a regulator of the cell cycle, transcription and endocrine receptor signalling [1]. 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 [2,3]. Pre-clinical HR+BC models indicate the potential for synergy when the CDK7 inhibitor samuraciclib is combined with the Selective Estrogen Receptor Degrader fulvestrant [4]Materials and Methods: This single arm cohort assessed the tolerability and efficacy of samuraciclib in combination with standard dose fulvestrant in patients with advanced HR+BC; all patients had previously received an aromatase inhibitor and a CDK4/6i 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 (QD) and 25 patients a dose of 360mg QD. 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 along with stratification data based on demographic factors such as hepatic involvement and cfDNA analysis (ESR1m, PI3Km).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.References:1.Patel et al., Mol Cancer Therap. 20182.Juric et al., SABCS 20183.Lindeman et al., JCO 20214.Jeselsohn et al., SABCS 2019 Citation Format: Charles Coombes, Sasha J Howell, Matthew G Krebs, Simon Lord, Laura M Kenny, Ash Bahl, Glen Clack, Edward Ainscow, Paul A Dickinson, Raluca Fostea, Janine Mansi, Carlo Palmieri, Gianflippo Bertelli, Rinath Jeselsohn, Zahi Mitri, William J Gradishar, Sagar Sardesai, Joyce O'Shaughnessy, Patrick Ward, Pavani Chalasani, Manfred Lehnert, Simak Ali, Stuart McIntosh. 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) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS3-10.