Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors.

ABSTRACT:

Background

Constitutive activation of ERK1/2 occurs in various cancers, and its reactivation is a well-described resistance mechanism to MAPK inhibitors. ERK inhibitors may overcome the limitations of MAPK inhibitor blockade. The dual mechanism inhibitor SCH772984 has shown promising preclinical activity across various BRAFV600/RAS-mutant cancer cell lines and human cancer xenografts.

Methods

We have developed an orally bioavailable ERK inhibitor, MK-8353; conducted preclinical studies to demonstrate activity, pharmacodynamic endpoints, dosing, and schedule; completed a study in healthy volunteers (P07652); and subsequently performed a phase I clinical trial in patients with advanced solid tumors (MK-8353-001). In the P07652 study, MK-8353 was administered as a single dose i

SUBMITTER: Moschos SJ 

PROVIDER: S-EPMC5916243 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature