The Food and Drug Administration (FDA) has approved Ayvakit (avapritinib; Blueprint Medicines Corporation), a tyrosine kinase inhibitor, for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.

The approval was based on data from the single-arm, open-label NAVIGATOR trial that assessed Ayvakit in 43 patients with GIST harboring a PDGFRA exon 18 mutation, including 38 patients with PDGFRA D842V mutation. Patients received Ayvakit once daily until disease progression or unacceptable toxicity; after an initial starting dose of 400mg, the recommended dose was later reduced to 300mg due to toxicity. The primary end point was overall response rate (ORR) based on independent radiological review using modified RECIST v1.1.

Findings from the study showed that patients with PDGFRA 18 exon mutation achieved an ORR of 84% (95% CI, 69-93) with 7% having complete response and 77% having partial response. For patients with PDGFRA D842V mutation, the ORR was 89% (95% CI, 75-97) with 8% having complete response and 82% having partial response. The study did not reach a median duration of response, but a response of ≥6 months was observed in 61% (n=22) of the responding patients with 18 exon mutations (11 patients with an ongoing response were followed <6 months from onset of response). 

Regarding safety, the most common treatment-emergent adverse events were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness. 


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“GIST harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST. However, today’s approval provides patients with the first drug specifically approved for GIST harboring this mutation,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “Clinical trials showed a high response rate with almost 85% of patients experiencing tumor shrinkage with this targeted drug.”

The Company offers financial assistance via co-pay and patient assistance programs found here. The product will be made available in the coming week in 100mg, 200mg, and 300mg tablets in 30-count bottles.

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