FDA Approves Avapritinib for Resectable or Metastatic Gastrointestinal Stromal Tumor

The FDA approved avapritinib for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumor harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations.

The FDA approved avapritinib (Ayvakit) for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842Vmutations.

The agent is the first precision therapy approved to treat a genomically defined population of patients with GIST.

“Today's approval of Ayvakit brings forward a new standard of care for patients with PDGFRA exon 18 mutant GIST, a genomically-defined population that previously had very limited treatment options. For the first time, we can offer these patients a highly effective treatment that targets the underlying genetic cause of their disease," Michael Heinrich, MD, professor of medicine at Oregon Health & Science University and an investigator on the NAVIGATOR trial, said in a press release. "Building on our growing understanding of the molecular basis of GIST, this milestone ushers in a new era of precision medicine in this disease. The FDA approval represents a call to action to conduct mutational testing in all patients with GIST before initiating kinase inhibitor therapy, as recommended by clinical guidelines, so appropriate patients may realize the benefits of this promising new medicine."

The approval is based on efficacy results from the phase I NAVIGATOR trial, as well as combined safety data from multiple studies of avapritinib. In the specific PDGFRA exon 18–mutant patient population, avapritinib elicited an 84% overall response rate (ORR; 95% CI, 69%-93%). The ORR comprised a 7% complete response (CR) rate and a 77% partial response (PR) rate. Specifically in patients with PDGFRA D842V mutations, the ORR was 89% (95% CI, 75%-97%), which included an 8% CR rate and an 82% PR rate. The median duration of response (DOR) was not reached in either patient population (range, 1.9+ months to 20.3+ months).

The most common (≥20%) adverse events (AEs) were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness.

"The full approval of Ayvakit based on robust data from our phase I NAVIGATOR clinical trial is an incredibly exciting milestone for our company and, more importantly, for GIST patients with a PDGFRA exon 18 mutation, who have been waiting for a new treatment option," Jeff Albers, chief executive officer at Blueprint Medicines, said in the release. "Ayvakit is the first of what we hope will be many approved medicines enabled by our research platform. Now, as we begin to deliver AYVAKIT to patients and their healthcare providers, we aim to fortify our leadership in the field of precision medicine and build a foundation for our broader portfolio by pairing our strong research and development capabilities with an equally talented commercial organization focused on addressing patient needs, accelerating diagnostic testing and enabling access."


Blueprint Medicines announces FDA approval of Ayvakit (avapritinib) for the treatment of adults with unresectable or metastatic PDGFRA exon 18 mutant gastrointestinal stromal tumor [news release]. Blueprint Medicines Corporation. Published January 9, 2020. https://bit.ly/2sTz3GX. Accessed January 9, 2020.