10/ Overall, our translational results underscore the therapeutic potential of PDGFRA inhibition with avapritinib in pHGG and DMG with distinct PDGFRA alterations, a patient cohort that currently faces a dismal prognosis.

9/ Lastly, we aimed to identify genetic predictors of response to avapritinib and propose alternative receptor tyrosine kinase pathway upregulation as a resistance mechanism, as illustrated in an avapritinib resistant tumor lesion that developed a novel EGFR amplification.

8/ Our early data demonstrate that avapritinib monotherapy is well tolerated and results in radiographic response in 3/7 cases, with best responses observed in patients with tumors harboring PDGFRA amplification or exon 18 mutation.

7/ Through wonderful clinical collaborations around the globe, we treated eight pediatric and young adult pHGG patients with avapritinib as a compassionate use and report first safety and response data in this patient population.

6/ We furthermore revealed efficient brain penetrance and prolonged survival in three PDGFRA-altered DMG models in vivo following oral avapritinib treatment.

5/ Among a panel of 2nd and 3rd generation TKIs, we identified the FDA-approved PDGFRA/KIT inhibitor avapritinib as selective against PDGFRA and highly effective against PDGFRA-altered patient-derived pHGG and DMG models in vitro.

4/ We detected PDGFRA activating mutations and/or gene amplifications in ~15% of pHGG cases, with high-level PDGFRA amplifications frequently found on extrachromosomal DNA.