Blueprint Medicines reports 'promising' proof-of-concept data from BLU-285 trial
Blueprint Medicines announced data from its ongoing Phase 1 clinical trial evaluating BLU-285, an investigational medicine for the treatment of patients with advanced gastrointestinal stromal tumors. These data provide proof-of-concept for BLU-285, a potent, highly selective inhibitor of D842V mutant PDGFRalpha and Exon 17 mutant KIT. The data will be presented on Thursday, December 1, 2016 at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany. "The clinical activity observed to date in the dose escalation portion of this Phase 1 study is promising," said Michael Heinrich, M.D., Oregon Health & Science University, an investigator for the clinical trial. "Advanced GIST is a devastating illness, marked by rapid disease progression. Seeing tumor shrinkage in 14 out of 15 PDGFRalpha-driven GIST patients at this point in the study is notable. I am also excited to see tumor shrinkage in four out of the six KIT-driven GIST patients treated at the higher dose levels, indicating the potential for increased clinical activity as we continue to dose-escalate. Given these encouraging early data for this investigational medicine, I believe BLU-285 could be transformative for patients with advanced GIST." BLU-285 is currently being evaluated in the dose escalation stage of a Phase 1 clinical trial in patients with unresectable PDGFRalpha-driven GIST and patients with treatment-resistant KIT-driven GIST. As of the data cutoff date of November 1, 2016, 36 patients had been treated in the dose escalation portion of the Phase 1 clinical trial at seven dose levels, including 18 patients with PDGFRalpha-driven GIST and 18 patients with KIT-driven GIST. The median age was 61, and the median number of prior tyrosine-kinase inhibitor regimens was 3.5. As of the data cutoff date of November 1, 2016, BLU-285 was observed to be well-tolerated at all doses. The majority of adverse events (AEs) reported by investigators were Grade 1 or 2. Across all grades, AEs reported by investigators most commonly included nausea, vomiting, peripheral edema, fatigue and constipation. Investigators reported treatment-related Grade 3 AEs in three patients: nausea and vomiting; anemia and intratumoral hemorrhage; and hypophosphatemia. No dose-limiting toxicities or drug-related Grade 4 or 5 AEs were reported, and no patients discontinued BLU-285 due to treatment-related adverse events. A maximum tolerated dose has not been reached, and enrollment in the dose escalation portion of the Phase 1 clinical trial is ongoing. Based on the favorable safety profile and encouraging clinical activity observed to date in the Phase 1 clinical trial for BLU-285 for the treatment of advanced GIST, Blueprint Medicines will continue to enroll patients in the dose escalation portion of this clinical trial until a MTD or a lower recommended dose for further clinical evaluation has been established. Enrollment in the expansion cohorts for this Phase 1 clinical trial is expected to begin in the first half of 2017. Blueprint Medicines plans to enroll approximately 35 patients with advanced GIST in the expansion cohorts. We also plan to accelerate our evaluation of expanded development options for BLU-285 in GIST, including opportunities to move to earlier lines of therapy and possible combinations.