Early Evidence Of Dose-Dependent Pharmacodynamic Activity Following Treatment With Sy-5609, A Highly Selective And Potent Oral Cdk7 Inhibitor, In Patients With Advanced Solid Tumors

Background: SY-5609 is an oral, noncovalent, highly selective, and potent inhibitor of CDK7, a key regulator of two fundamental processes important in cancer: transcription and cell cycle control. Preclinical in vivo studies identified a pharmacodynamic (PD) gene expression marker, POLR2A mRNA, associated with SY-5609 dose-dependent tumor growth inhibition (TGI). A phase 1 single-agent dose-escalation study of SY-5609 initiated in January 2020 in patients (pts) with advanced breast, colorectal, lung or ovarian cancer, or solid tumors with Rb pathway abnormalities. Dose escalation of SY-5609 in combination with fulvestrant in hormone receptor positive (HR+) breast cancer pts after CDK4/6 inhibitor treatment failure began in June 2020. We report early results from the initial pts with a focus on tolerability, safety, pharmacokinetics (PK) and PD.