Abstract 265P
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. References: 1. Juric D et al., SABCS 2018; 2. Baselga J et al. Lancet Oncol 2017; 3. Jeselsohn et al., SABCS 2019.
Clinical trial identification
2017-00202620.
Editorial acknowledgement
Legal entity responsible for the study
Carrick Therapeutics.
Funding
Carrick Therapeutics.
Disclosure
M.G. Krebs: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Seattle Ger; Financial Interests, Personal, Advisory Board: OM Pharma; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Other, Travel expenses: BerGenBio; Financial Interests, Personal, Other, travel expenses: Immutep; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BerGenBio; Financial Interests, Personal, Advisory Board: Achillies Therapeutics; Financial Interests, Institutional, Principal Investigator: Carrick; Financial Interests, Institutional, Principal Investigator: Turning Poi; Financial Interests, Institutional, Principal Investigator: Janssen; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Blueprint; Financial Interests, Institutional, Principal Investigator: BerGenBio; Financial Interests, Institutional, Principal Investigator: Immutep; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: Seattle Ger. A. Bahl, G. Clack: Financial Interests, Personal, Full or part-time Employment: Carrick Therapeutics; Financial Interests, Personal, Stocks/Shares: Carrick Therapeutics. E. Ainscow: Financial Interests, Personal, Stocks/Shares: Carrick Therapeutics; Financial Interests, Personal, Full or part-time Employment: Carrick Therapeutics; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Lehnert: Financial Interests, Personal, Stocks/Shares: Carrick Therapeutics. S. Ali: Financial Interests, Personal, Stocks/Shares: Carrick Therapeutics; Non-Financial Interests, Institutional, Full or part-time Employment: IMperial College Hospital. S. McIntosh: Financial Interests, Personal, Stocks/Shares: Carrick Therapeutics; Financial Interests, Personal, Full or part-time Employment: Carrick Therapeutics. R.C. Coombes: Financial Interests, Personal, Stocks/Shares: Carrick Therapeutics. All other authors have declared no conflicts of interest.