Introduction
TNBC, cancer, cancers, breast cancer
DISEASE, CANCER, CANCERS, BREAST CANCER
Cyclin-dependent kinases (CDKs) are rational targets for cancer therapy due to their important roles in cell division and transcriptionPre-clinical studies have demonstrated the sensitivity of many cancers to selective inhibitors of CDK7This modular Phase I study was designed to establish the optimal dose of samuraciclib when used as monotherapy or in combination with other anti-cancer treatments. The results from dose escalation and 2 expansion cohorts in breast cancer are presented here. Module 1A was a first-in-human dose escalation study to assess initial safety, tolerability and the PK profile of samuraciclib and to identify the maximum tolerated dose (MTD). Module 1 Part B, Part 1 in TNBC (Module 1B-1), was designed to refine the safety, tolerability, PK, and pharmacodynamic profiles of samuraciclib monotherapy (360 mg once daily [OD]) in patients who had received prior systemic therapy for advanced TNBC. Module 2A explored the safety, tolerability and preliminary efficacy of 2 dose levels of samuraciclib (240 mg OD and 360 mg OD) in combination with fulvestrant in HR+/HER2− advanced breast cancer patients who had previously received CDK4/6 inhibitor therapy.In this work, samuraciclib has an acceptable safety profile and initial evidence of efficacy is demonstrated as a selective inhibitor of CDK7. Samuraciclib has the potential to address the significant medical need of patients whose disease has progressed on CDK4/6 inhibitors and will be investigated further in future studies.