INCB123667

INCB123667 is a novel, potent, and selective oral small molecule inhibitor of cyclin-dependent kinase 2 (CDK2). It is being developed by Incyte for the treatment of advanced or metastatic solid tumors. The drug acts by inhibiting CDK2/cyclin E1 activity with subnanomolar potency, leading to suppression of tumor growth as monotherapy and in combination with standard-of-care therapies. Preclinical studies have shown significant single-agent antitumor activity in CCNE1-high breast cancer xenograft models and inhibition of retinoblastoma protein phosphorylation. Mechanistically, it blocks the G1-S cell cycle transition and induces cell growth inhibition in cancer cells characterized by cyclin E amplification or CCNE1 overexpression. Clinical development is ongoing with Phase 1 trials evaluating safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy across multiple solid tumor types including breast cancer, ovarian cancer, gastrointestinal cancers, uterine cancers, endometrial cancer, peritoneal cancer, carcinosarcoma, papillary adenocarcinoma/carcinoma/sarcoma/esophageal/clear cell sarcoma/adenocarcinoma[1][3][4][5][6].