vepdegestrant + samuraciclib

Vepdegestrant + samuraciclib is an investigational oral combination therapy for advanced or metastatic estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer, targeting patients who have previously progressed after CDK4/6 inhibitor therapy. Vepdegestrant (ARV-471) is a *PROTAC® estrogen receptor (ER) degrader* designed to selectively bind and promote degradation of the estrogen receptor via the proteasome pathway, reducing ER-driven tumor activity. Samuraciclib (CT7001) is a *first-in-class oral inhibitor of cyclin-dependent kinase 7 (CDK7)*, which regulates cell cycle progression and transcription, impacting tumor cell proliferation. The combination aims to provide effective ER pathway suppression alongside inhibition of the CDK7-regulated cell cycle, for a potentially enhanced anti-tumor response in patients resistant to prior endocrine and CDK4/6 inhibitor therapy. The combination is currently under investigation in Phase 1b/2 clinical trials (e.g., TACTIVE-U Sub-Study C) to evaluate safety, dose, and efficacy in collaboration between Carrick Therapeutics, Arvinas, and Pfizer[1][3][5].