{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gallagher P"],"funding":["FP7 Health"],"pagination":["17"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11947101"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["3(1)"],"pubmed_abstract":["<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-f"],"journal":["BJC reports"],"pubmed_title":["A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers."],"pmcid":["PMC11947101"],"funding_grant_id":["602901"],"pubmed_authors":["Elez E","Lawler M","Bardelli A","Van Schaeybroeck S","Laurent-Puig P","Peeters M","Taieb J","Delfavero J","Rolfo C","Bettens K","Perkins G","Coyle V","Grayson M","Boyd R","Maughan TS","Gallagher P","Salto-Tellez M","Aroldi F","Popovici V","Tabernero J","Prenen H","Carson R","Houlden J","Khawaja H","Hennessy BT","Roberts C","MErCuRIC Trial Consortium","Wilson RH","Adams R","Middleton MR","Collins L","Di Nicolantonio F","Jones R","Andre T"],"additional_accession":[]},"is_claimable":false,"name":"A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers.","description":"<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-f","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-04-08T18:40:31.574Z","creation":"2025-07-04T03:05:43.139Z"},"accession":"S-EPMC11947101","cross_references":{"pubmed":["40140597"],"doi":["10.1038/s44276-025-00133-6"]}}