GVV858

GVV858 is an investigational small molecule inhibitor of cyclin-dependent kinase 2 (CDK2) being developed by Novartis. It is specifically designed to target tumors that exhibit CCNE1 (Cyclin E1) amplification or those that have developed resistance to CDK4/6 inhibitors, such as palbociclib or ribociclib. CCNE1 amplification leads to the overactivation of CDK2, which drives uncontrolled cell proliferation and is a known mechanism of resistance in hormone receptor-positive breast cancer. By selectively inhibiting CDK2, GVV858 induces cell cycle arrest at the G1/S phase transition. The drug is currently undergoing Phase 1/2 clinical evaluation as a monotherapy and in combination with endocrine therapies (fulvestrant or letrozole) for advanced HR+/HER2- breast cancer, metastatic castration-resistant prostate cancer, and other CCNE1-amplified solid tumors.