Early news on a Merck drug candidate has researchers hopeful that the investigational therapy could be used to fight drug resistant cancers. The data is early — and on a very small patient group — but researchers say the drug’s performance matches initial response rates to approved treatments like MEK inhibitors.
The treatment, called MK-8353, was tested in patients with melanoma and other cancers with mutations in the BRAF or RAS genes. The drug was designed to block the ERK signal, which has been shown to help drive cancer cell growth in resistant melanoma and other diseases.
While targeted treatments have been approved for melanoma and lung cancers with a specific mutation in the BRAF gene, most patients develop resistance to these treatments, and their cancer comes back, most commonly due to ERK reactivation.
To tackle the resistance problem, researchers at University of North Carolina Lineberger and other institutions investigated MK-8353 to block ERK. Results from the Phase I study were published by UNC Lineberger’s Stergios Moschos and his colleagues.
“ERK certainly stimulates factors that promote cancer growth,” Channing Der, a professor at UNC School of Medicine Department of Pharmacology, said in a statement. “ERK is very complex, and it’s still surprisingly poorly understood, but what is very clear is that it is required for cancer growth, and that’s why there are a number of inhibitors in this pathway that are either approved, or under clinical evaluation.”
In this new study, three of the 15 patients who had results that could be evaluated experienced partial responses to the investigational treatment. Researchers noted that although their study included a small number of patients, this response rate was similar to rates seen in studies of other treatments.
“The response rate that we saw for ERK inhibitors is reminiscent of the response seen with MEK inhibitors,” Moschos said. “We think, therefore, that ERK inhibitors cannot be given as single agents, just like MEK inhibitors. The question is: Which combination is best?”
The UNC trial was part of a larger effort looking at the potential of ERK inhibitors in treating different cancers. Merck is currently testing MK-8353 along with its immuno-oncology drug Keytruda in a Phase Ib trial recruiting patients with advanced tumors.
Image: UNC Lineberger’s Stergios Moschos. UNC Lineberger