First-in-Human Phase I/IIa Study of the First-in-Class CDK2/4/6 Inhibitor PF-06873600 Alone or with Endocrine Therapy in Patients with Breast Cancer.

ABSTRACT:

Purpose

The discovery that cyclin E overexpression is a key cyclin-dependent kinase (CDK) 4/6 inhibitor resistance mechanism has reinvigorated interest in targeting CDK2 and the simultaneous inhibition of CDK2/4/6 as a novel therapeutic approach. This first-in-human study assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of PF-06873600, the first-in-class inhibitor of CDK2/4/6.

Patients and methods

Dose escalation included 78 patients with advanced breast cancer, triple-negative breast cancer, or ovarian cancer who received oral PF-06873600 at doses ranging from 1 to 50 mg twice daily (part 1A, n = 51) or PF-06873600 with endocrine therapy (part 1B, n = 16; part 1C, n = 11) to determine the recommended dose for expansion (RDE). Dose expansio

SUBMITTER: Yap TA 

PROVIDER: S-EPMC12260505 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature