Ulixertinib A First-in-class ERK Inhibitor Shows Early Efficacy
CancerConnect News: The novel ERK1/2 kinase inhibitor ulixertinib displayed an acceptable safety profile and had clinical activity in patients whose cancers had mutations in the MAPK cell-signaling pathway, according to data from a recent phase 1 clinical trial. Based on data from this trial, ulixertinib has received the U.S. Food and Drug Administration’s Fast Track designation.
In recent years precision cancer medicine has led to improved treatments for melanoma, lung, colon, breast, and other cancer types. A great number of cancers, including melanoma and lung cancers, have mutations in the MAPK/ERK pathway, and while current therapies target proteins in this cascade, many patients develop resistance to current drugs.
The purpose of precision cancer medicine to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic **& genomic testing,**including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells.
The ERK gene is the final regulator in the MAPK/ERK pathway, and when upstream inhibition of this protein cascade fails, ERK signaling is reactivated, resulting in renewed MAPK signaling. Targeting ERK for inhibition may allow the opportunity to thwart resistance from upstream mechanisms.
Doctors recently reported results from a early phase clinical trial evaluating the ERK inhibitor ulixertinib. They enrolled 27 patients in a dose-escalation phase and 108 in the dose-expansion phase. All patients had advanced solid cancers and more than 65 percent had BRAF-mutant cancers. Twenty-four percent of patients had received prior BRAF and/or MEK therapy and 51 percent had received prior immunotherapy. Overall partial responses were seen in 12 percent and 14 percent of evaluable patients in the dose-escalation and dose-expansion groups respectively. The study demonstrates that ulixertinib is tolerable and has activity in a subset of patients with mutations in the MAPK pathway. Based on this promising activity ulixertinib has been given fast track designation by the FDA and will undergo further evaluation in a variety of cancers.
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