Promising anti-tumour activity of the CDK7-inhibitor samuraciclib plus fulvestrant

Efficacy of second-line treatment options for patients with oestrogen receptor (ER)-positive/HER2-negative metastatic breast cancer who progress on an aromatase inhibitor plus CDK4/6 inhibitor is poor. In a first-in-human, phase 2 trial, samuraciclib in combination with fulvestrant showed promising activity.

At the moment, there is no current agreed standard of care treatment for woman with ER-positive/HER2-negative metastatic breast cancer who progress on first-line treatment with CDK4/6 inhibitor plus aromatase inhibitor or selective oestrogen receptor degrader (SERD) [1-3]. CDK7 inhibition is a promising therapeutic strategy in cancer because it acts as a regulator of the cell cycle, transcription, and endocrine receptor signalling. Pre-clinical breast cancer models indicate the potential for synergy when the CDK7 inhibitor samuraciclib is combined with fulvestrant [4].

Prof. Charles Coombes (Imperial College London, UK) presented the results of a first-in-human, phase 2 trial with samuraciclib plus fulvestrant [5]. This single arm cohort assessed the tolerability and efficacy of samuraciclib in combination with standard dose fulvestrant in 31 patients with metastatic ER-positive/HER2-negative breast cancer who had previously received an aromatase inhibitor and a CDK4/6 inhibitor for advanced disease. The combination treatment was generally well tolerated, with adverse drug reactions of note being grade 1–2 nausea, vomiting, and diarrhoea. Most patients stayed on treatment until disease progression. No neutropenia was observed. Clinical benefit rate at 24 weeks was 36%. Clinical benefit rate in TP53 wildtype patients was 53%. Median progression-free survival for TP53 wildtype patients was 32 weeks versus 7.9 weeks for TP53 mutant patients. In addition, liver metastases were a negative predictive factor: median progression-free survival for patients without liver metastases was over 48 weeks versus 11.9 weeks for patients with liver metastases.

“These first results demonstrate that samuraciclib has an acceptable safety profile with evidence of anti-tumour activity in combination with fulvestrant for patients with metastatic ER-positive/HER2-negative breast cancer who have progressed on their prior CDK4/6 inhibitor,” concluded Prof. Coombes.

1. Cook MM, et al. Oncologist 2021;26:101–106.


2. Rugo HS, et al. Lancet Oncol 2021;22:489–498.


3. Lindeman GJ, et al. J Clin Oncol 2021;39(Suppl):1004.


4. Patel H, et al. Mol Cancer Therap 2018;17:1156–1166.


5. Coombes C, et al. 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). GS3-10, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January, 2022