Avapritinib Approved by the FDA for Treatment of PDGFRA 18+ GIST

The FDA has approved avapritinib (Ayvakit) for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) who harbor platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, includingPDGFRAD842V mutations. This approval makes avapritinib the first precision medicine therapy for a genomically defined population of patients with GIST, according to a press release from the Blueprint Medicines Corporation.

Avapritib was approved based on results from the phase I NAVIGATOR trial (NCT02508532) which showed durable responses in 43 patients withPDGFRAexon 18 mutations. The overall response rate (ORR) in these patients was 84% and of those responses, 7% were complete responses (CRs) and 77% were partial responses (PRs). In patients withPDGFRAD842V mutations, the ORR was 89% (95% CI: 75 —97). Of these overall responses, 8% were CRs and 82% were PRs. The median duration of response was not reached in either group of patients.

In the 204 evaluated patients, there were no safety contradictions observed with avapritinib. The most common adverse events were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness. These AEs occurred in ≥20 of the patients.

“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,” said Michael Heinrich, MD, professor of medicine at Oregon Health & Science University and an investigator on the NAVIGATOR trial in a statement.

The primary end point is ORR. The key secondary end points of the study include progression-free survival, DOR, and clinical benefit rate.

To be eligible for enrollment in the study, individuals must have had a confirmed diagnosis of unresectable GIST that progressed following imatinib and been treated with at least 1 of the following: sunitinib (Sutent), regorafenib (Stivarga), sorafenib (Nexavar), dasatinib (Sprycel), pazopanib (Votrient), or an experimental kinase-inhibitor agent. Additionally, the patient could not have a D842V mutation in thePDGFRAgene, at least 1 measurable lesion, and an ECOG performance status of 0 to 2.

Patients were excluded if they had a platelet count <90,000/mL, an absolute neutrophil count <1000/mL, or the presence of medical conditions that may have interfered with treatment in the study.

&ldquo;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,&rdquo; Heinrich said.

Reference:

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]. Cambridge, Massachusetts: Clueprint Medicines Corporation; January 9, 2020.http://ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-announces-fda-approval-ayvakittm-avapritinib. Accessed January 9, 2020.