Blueprint Medicines 'encouraged' by early Phase 1 BLU-554 trial data
Blueprint Medicines Corporation announced data from its ongoing Phase 1 trial evaluating BLU-554, an investigational medicine for the treatment of advanced hepatocellular carcinoma. Blueprint Medicines is developing BLU-554 as a potent, highly selective inhibitor of fibroblast growth factor receptor 4. The data are being presented on Tuesday, November 29, 2016, at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany. "We are very encouraged to see early anti-tumor activity in patients with confirmed FGF19 overexpression and consistent evidence of FGFR4 pathway modulation during the dose escalation part of this first-in-human clinical trial," said Andy Boral, M.D., Chief Medical Officer of Blueprint Medicines. "Now that we have demonstrated proof-of-concept, determined the maximum tolerated dose, and implemented FGF19 biomarker screening globally, we can move rapidly to enroll patients in the expansion part of the study to more fully evaluate the activity of BLU-554 in patients with advanced HCC." BLU-554 was evaluated in the dose escalation stage of a Phase 1 clinical trial in patients with advanced HCC. As of the data cutoff date of November 7, 2016, 25 patients had been treated in the dose escalation portion of the Phase 1 clinical trial at five dose levels, with the majority of patients having previously received sorafenib. The study was designed to retroactively assess patient biopsies for FGFR4 pathway activation after enrollment by evaluating levels of FGF19, the protein that activates FGFR4, using an investigational immunohistochemistry assay. Prospective screening of patients with the investigational IHC assay was implemented during dose escalation, enabling enrollment of enrichment patients with confirmed FGF19 overexpression which resulted in a larger number than anticipated of biomarker positive patients being enrolled. Blueprint Medicines has initiated the expansion portion of the Phase 1 clinical trial, and enrollment is ongoing. Pharmacokinetic data across all dose levels showed rapid oral absorption, a mean half-life of approximately ten hours, and exposure in the expected therapeutic range based on HCC xenograft models. Blueprint Medicines has initiated enrollment of the biomarker-selected expansion cohorts at the maximum tolerated dose of 600 mg QD. In the expansion, patients will be prospectively evaluated for tumor expression of FGF19 using an investigational IHC assay. We plan to enroll approximately 45 patients in three subsets. Two subsets of patients will be selected to have tumors that overexpress FGF19, which indicates autocrine physiology, where FGF19 is produced by the tumor cells in the liver. One of the patient subsets with tumors that overexpress FGF19 will also have FGF19 gene amplification. The third subset of patients will be selected to have tumor FGF19 expression less than 1% by the IHC assay, which indicates normal endocrine physiology, where FGF19 is produced by the intestine.