"We have very few examples of drugs entering brain tumors like this and shutting down key oncogenic pathways. These results support a lot of ongoing efforts to build on the success of avapritinib and other brain penetrant small molecule inhibitors," said Carl Koschmann, M.D., Research Professor in the Department of Pediatrics at the University of Michigan, in a press release.
Avapritnib has been approved to treat advanced systemic mastocytosis and indolent systemic mastocytosis and gastrointestinal stromal tumors with a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation. Previous research indicates that PDGFRA plays a crucial role in high-grade gliomas, suggesting its potential suitability as a therapeutic target for the condition.
In the current study, researchers investigated avapritinib as a potential treatment for high-grade glioma. In experiments in mouse models of the condition, the drug successfully crossed the blood-brain barrier and significantly reduced tumor growth. The drug also significantly extended the survival time of the mice.
The researchers were also able to treat eight pediatric and young adult patients with predominantly recurrent/refractory PDGFRA-altered high-grade glioma via an expanded access program. Early data suggests that the drug was well-tolerated, and that tumors shrunk in three patients.
The findings helped pave the way to include pediatric high-grade glioma in a phase I pediatric solid tumor trial, which has completed accrual and is currently under analysis.
"We know a single drug is not going to be enough for this disease. The way to make true progress will be combining many different types of modalities, like combining drugs that are target pathways activated by the first drug. We already have a follow-up story on targeting avapritinib with MAP kinase inhibitors that we are just as excited about,” said Koschmann.
Sources: Science Daily, Cancer Cell
