biostudies-literatureGallagher PFP7 Health17https://www.ebi.ac.uk/biostudies/studies/S-EPMC11947101biostudies-literatureUnknown3(1)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Twenty-fBJC reportsA phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers.PMC11947101602901Elez ELawler MBardelli AVan Schaeybroeck SLaurent-Puig PPeeters MTaieb JDelfavero JRolfo CBettens KPerkins GCoyle VGrayson MBoyd RMaughan TSGallagher PSalto-Tellez MAroldi FPopovici VTabernero JPrenen HCarson RHoulden JKhawaja HHennessy BTRoberts CMErCuRIC Trial ConsortiumWilson RHAdams RMiddleton MRCollins LDi Nicolantonio FJones RAndre TfalseA phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Twenty-f2025-01-01T00:00:00Z2025 Mar2026-04-08T18:40:31.574Z2025-07-04T03:05:43.139ZS-EPMC119471014014059710.1038/s44276-025-00133-6