A phase 1/2 clinical study of avapritinib (Ayvakit®) in patients with advanced gastrointestinal stromal tumor (GIST) demonstrated its safety and anti-tumor activity.

The results were reported by CStone Pharmaceuticals, a biopharmaceutical company researching and developing avapritinib with Blueprint Medicines, at the virtual European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2021.

The open-label, multicenter study evaluated the safety, pharmacokinetics, and efficacy of avapritinib in Chinese patients with unresectable or metastatic GIST. The treatment demonstrated significant anti-tumor activity in patients with GIST carrying a D842V mutation in platelet-derived growth factor receptor alpha (PDGFRA), who have a poor prognosis and remission rate with existing tyrosine kinase inhibitor therapies. Avapritinib treatment resulted in an objective response rate (ORR) of 70% and the clinical benefit rate (CBR) was 80%.


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In addition, avapritinib showed moderate anti-tumor activity (ORR of 17% and CBR of 52%) in patients who have already been treated with 3 or more therapies, supporting its potential as a fourth or later line of treatment for GIST patients. In these patients, the median progression-free survival (PFS) was 5.6 months.

Avapritinib was well-tolerated, CStone reported, with treatment-emergent adverse events including anemia, decreased white blood cell count, decreased neutrophil count, increased blood bilirubin, increased blood creatine phosphokinase, increased aspartate aminotransferase, face edema, eyelid edema, and hair color changes.

“Due to the extremely limited benefits from existing therapies, patients with PDGFRA D842V mutant GIST have high medical needs,” said Said Lin Shen, principal investigator of the study: “Ayvakit has shown a well-tolerated safety profile, and brings an important additional treatment option to patients.”

GIST is a type of tumor that occurs in the tissues in the wall of the gastrointestinal tract, most commonly in the stomach or small intestine. About 10% of cases are associated with a mutation in the PDGFRA gene that codes for PDGFRA, a receptor tyrosine kinase found in the cell membrane of certain cells. Around 5% to 6% of cases are caused by a PDGFRA D842V mutation. 

Avapritinib is a potent and selective oral inhibitor of the mutated PDGFRA. It is approved in the US for treatment of adults with unresectable or metastatic GIST harboring a mutation in the exon 18 of PDGFRA, including PDGFRA D842V mutation, and in the European Union for adults with unresectable or metastatic GIST harboring a PDGFRA D842V mutation.