Blueprint Medicines presented new preclinical data on its drug candidate, BLU-285, and its potential value in treatment-resistant GIST and on novel cancer drug targets at the AACR (American Association for Cancer Research) Annual Meeting in Philadelphia this past week.
BLU-285 is a targeted therapy that acts as a potent inhibitor of PDGFRa D842V and KIT Exon 17 mutants that play a key role in GIST (Gastrointestinal Stromal Tumors). BLU-285 showed significant anti-tumor activity in treatment-resistant models of GIST and in one mouse model maintained complete tumor regression in all mice treated at the highest dosage level.
Potential Significance for D82V Mutations
This is potentially significant as the D842V mutation that occurs in exon 18 of the PDGFRa gene represents almost two-thirds of the PDGFRa mutations that occur in GIST. D842v mutations are rare, occurring in about five percent of GIST patients.
Mutations in the KIT and PDGFRA gene are the most frequent genetic events that drive the biology of GIST tumors. Targeting these defects remains the primary drug therapy for GIST. While KIT mutations are much more common, PDGRFa mutations still represent a significant percentage of GISTs. D842Vmutations occur in exon 18, and are insensitive to Gleevec, Sutent and Stivarga.
This makes the management of patients with PDGFRA mutations more complex.
The preclinical information on BLU-285 holds promise for future targeted therapies for GIST patients who currently have no effective treatment options.
Blueprint Medicines will file an Investigational New Drug (IND) Application and will begin a Phase 1 Clinical trial of BLU-s85 in mid-2015.
We will be watching as information develops and will update the website as more information becomes available.