The US Food and Drug Administration (FDA) has accepted Blueprint Medicines' Investigational New Drug (IND) applications to begin phase 1 clinical trials for its two lead drug candidates: BLU-554 for the treatment of advanced hepatocellular carcinoma (HCC) and cholangiocarcinoma, and BLU-285 for unresectable, treatment-resistant gastrointestinal stromal tumour (GIST).

Blueprint Medicines is also on track to file an IND for BLU-285 in systemic mastocytosis.

"We are delighted to reach this important milestone in the development of our two lead drug candidates to meet the urgent needs of patients facing a poor prognosis and few, if any, viable treatment options," said Jeffrey Albers, chief executive officer of Blueprint Medicines.

"This achievement is a testament to our team's ability to execute on our stated goal of simultaneously advancing multiple programmes into clinical trials. Our powerful drug discovery engine continues to consistently generate highly selective kinase inhibitors against previously unaddressed genomic drivers of disease."

BLU-554 is a potent and selective inhibitor of fibroblast growth factor receptor 4 (FGFR4). Aberrant signaling of FGFR4 is a disease driver in up to 30 per cent of HCC patients and may also play a role in a subset of patients with cholangiocarcinoma, a related cancer of the biliary duct. HCC is the most prevalent form of liver cancer. Liver cancer is the second-leading cause of cancer-related deaths worldwide.

In this phase 1 trial, Blueprint Medicines expects to enroll 50 patients with advanced, unresectable HCC and an additional 10 patients with advanced, unresectable cholangiocarcinoma. The trial will enroll patients at multiple centres in the US, EU and Asia.

The trial will test the safety and tolerability of escalating doses of BLU-554, with the goal of establishing a maximum tolerated dose (MTD), or a recommended dose if the MTD is not achieved. Once the MTD or recommended dose has been established, HCC and cholangiocarcinoma patients with aberrant FGFR4 signaling will be enrolled in disease-specific expansion cohorts. Additional study objectives include the assessment of early signs of biological and clinical activity using disease-specific biomarkers and response rate measurement according to Response Evaluation Criteria In Solid Tumours (RECIST).

BLU-285 is a potent and selective inhibitor of KIT Exon 17 and PDGFR-alpha D842V mutants, which are key disease drivers of metastatic and treatment-resistant GIST. GIST is the most common form of sarcoma of the gastrointestinal tract. Patients with the KIT Exon 17 and PDGFR-alpha D842V mutants are not adequately treated with existing therapies.

In this phase 1 trial, Blueprint Medicines plans to enroll 60 patients with GIST or other relapsed or refractory solid tumours at multiple sites in the US, EU and Asia. The trial will test the safety and tolerability of escalating doses of BLU-285, with the goal of establishing an MTD, or a recommended dose if the MTD is not achieved. Once the MTD or recommended dose has been established, patients with treatment-resistant GIST and PDGFR-alpha D842V mutant GIST will be enrolled in expansion cohorts. Additional study objectives include assessing early signs of biological activity using disease-specific biomarkers and clinical efficacy as measured by response rate by RECIST modified for GIST.

Blueprint Medicines is a patient-driven oncology company developing highly selective kinase inhibitors for genomically defined cancer subsets.