The CDx test kit will use a real-time PCR fluorescent probe, along with specific primers, Taqman probes, and Taq enzymes, to detect the mutation in DNA samples


Avapritinib is a kinase inhibitor discovered by CStone’s partner Blueprint Medicines.(Credit: Belova59 from Pixabay.)

Genetron and its partner CStone Pharmaceuticals have commenced a clinical trial in China, to jointly develop a companion diagnostic (CDx) test for avapritinib.

Discovered by Blueprint Medicines, Avapritinib is a US Food and Drug Administration (FDA) approved kinase inhibitor, to treat unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations.

Also, the drug has received FDA breakthrough therapy designation for the treatment of advanced and indolent systemic mastocytosis (SM), and SM with hematologic neoplasm and mast cell leukaemia.

CStone and Blueprint Medicines collaborated for the development and commercialisation of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau, and Taiwan.

The collaboration is aimed at enhancing the commercial potential and benefits to patients, and promoting the development of precision medicine for GIST.

Genetron and CStone will develop a CDx kit to detect D842V mutation in PDGFRA gene

Under the partnership, Genetron Health and CStone are expected to co-develop a CDx kit to detect the D842V mutation in the human platelet-derived growth factor receptor alpha (PDGFRA) gene, using a polymerase chain reaction (PCR)-based method.

The CDx test kit will be designed to use a real-time PCR fluorescent probe, along with specific primers, Taqman probes, and highly specific Taq enzymes, to detect the mutation with high specificity and sensitivity in DNA samples.

Data from the Phase 1/2 bridging study showed that avapritinib was well tolerated in Chinese patients, with a safety profile consistent with previously established results in global studies.

Preliminary results demonstrated the robust clinical activity of avapritinib in Chinese patients with GIST harboring the PDGFRA D842V mutation, with 62.5% overall response rate (ORR).

The test has been validated by the China’s National Medical Products Administration (NMPA) and is now being used in this multi-centre clinical trial in China. NMPA’s Centre for Drug Evaluation (CDE) has accepted the regulatory application for priority review.

CStone has filed a New Drug Applications for avapritinib in PDGFRA exon 18 mutant gastrointestinal stromal tumors (GIST) with regulatory agencies in Taiwan and Mainland China, in 2020.