A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers.

ABSTRACT:

Background

Single-agent MEK1/2 inhibition has been disappointing in clinical trials targeting RAS mutant (MT) cancers, probably due to upstream receptor activation, resulting in resistance. We previously found that dual c-MET/MEK1/2 inhibition attenuated RASMT colorectal cancer (CRC) xenograft growth. In this study, we assessed safety of MEK1/2 inhibitor PD-0325901 with c-MET inhibitor crizotinib and determined the optimal biological doses for subsequent clinical trials.

Methods

In this dose-escalation phase I trial, patients with advanced solid tumours received PD-0325901 with crizotinib, using a rolling-6 design to determine the maximum tolerable dose (MTD) and safety/tolerability. Blood samples for pharmacokinetics and skin biopsies were collected.

Results

Twenty-f

SUBMITTER: Gallagher P 

PROVIDER: S-EPMC11947101 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature