First-In-Human Phase 1 Safety, Pk, And Pd Study Of The Cdk4/6 Inhibitor G1t28.

2527 Background: G1T28 is a highly potent and selective CDK4/6 inhibitor being developed as an IV agent for targeted bone marrow chemoprotection and as an oral antineoplastic agent. The CDK4/6 pathway is critical in regulating cell proliferation of certain tumors. In addition, hematopoietic stem and progenitor cells (HSPCs) are dependent upon CDK4/6 for proliferation. Transient G1T28-induced G1 cell cycle arrest of HSPCs renders them resistant to the cytotoxic effects of chemotherapy. Thus, G1T28 could be used for chemoprotection (reduction of chemotherapy-induced myelosuppression) in patients with CDK4/6-independent tumors, or as an antineoplastic agent in patients with CDK4/6-dependent tumors. Methods: The objective of this study was to assess the safety and tolerability of G1T28, as well as to characterize PK and PD (NCT02243150). Part 1 was a double blind, placebo-controlled, single escalating dose study in healthy volunteers of both sexes, where subjects were randomized (3:1) to receive G1T28 or plac...