FDA Approves Ayvakit for Gastrointestinal Stromal Tumor with a Rare Mutation

On January 9, 2020, the FDA approved avapritinib (Ayvakit; Blueprint Medicines), a kinase inhibitor, for the treatment of adult patients 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 FDA designated avapritinib as a breakthrough therapy and an orphan drug. Avapritinib was also granted Fast Track designation.

This approval was based on combined safety data from several clinical trials and efficacy data from the multicenter, single-arm, open-label, phase 1 NAVIGATOR clinical trial of 43 patients with GIST harboring PDGFRA exon 18 mutations, including 38 patients with the D842V mutation. Data were evaluated by independent reviewers using modified Response Evaluation Criteria in Solid Tumors v1.1 criteria for GIST.

In the NAVIGATOR trial, patients were treated with avapritinib 300 mg or 400 mg once daily until disease progression or unacceptable toxicity. The recommended dose was determined to be 300 mg once daily. The primary end point was overall response rate (ORR). Treatment with avapritinib resulted in ORR of 84% (7% complete response [CR]; 77% partial response [PR]) in patients harboring PDGFRA exon 18 mutations. In the subgroup of patients with PDGFRA D842V mutations, the ORR was 89% (8% CR; 82% PR). Median duration of response was not reached. Of the responding patients, 61% of those with PDGFRA exon 18 mutations had a response lasting ≥6 months (31% of patients with an ongoing response were followed for <6 months).

“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.

The most common (≥20%) adverse reactions with avapritinib 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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