BLU-285 FOR UNRESECTABLE, TREATMENT-RESISTANT GASTROINTESTINAL STROMAL TUMORS (GIST)

BLU-285 is an oral, investigational drug being studied for safety and clinical activity in patients with metastatic and treatment-resistant gastrointestinal stromal tumors (GIST). BLU-285 inhibits PDGFRα D842V and KIT Exon 17 mutants which play a key role in GIST.

Although treatment options for people with GIST have improved in recent years, there remains a significant unmet need among patients with these mutations. For patients with GIST driven by the PDGFRα D842V mutant, there is no effective therapy. For patients with KIT-driven GIST, current treatments can be very effective, but over time, cancer cells often become resistant to currently approved therapies, leading to recurrence of the disease.

We have successfully completed preclinical studies demonstrating significant anti-tumor activity, including tumor regression, in a disease model of GIST that is refractory to treatment with imatinib.

We have initiated a  Phase 1 clinical trial for BLU-285 for the treatment of patients with unresectable, treatment-resistant GIST, and we are currently enrolling patients. The Phase 1 clinical trial will evaluate the safety and tolerability of BLU-285 in multiple ascending doses in patients with unresectable, treatment-resistant GIST with the goal of establishing a maximum tolerated dose (MTD) or a recommended dose if the MTD is not achieved.

To learn more about this clinical trial, please click here.

 

 

BLU-285 FOR ADVANCED SYSTEMIC MASTOCYTOSIS

BLU-285 is an oral, investigational drug being studied for safety and clinical activity in patients with advanced systemic mastocytosis (SM), including aggressive SM, SM with associated clonal hematological non-mast cell disorders (SM-AHNMD) and mast cell leukemia (MCL). BLU-285 is a potent and highly selective inhibitor of the KIT D816V mutant, the primary driver of disease in more than 94 percent of SM patients.

SM is characterized by the abnormal accumulation of mast cells. In patients with severe forms of the disease, mast cells accumulate in organs, such as the bone marrow, spleen and liver, compromising organ function. There are no approved targeted therapies for SM patients with KIT D816V-driven disease.

We have successfully completed preclinical studies demonstrating significant anti-tumor activity and disease control in disease models of SM.

We have initiated a Phase 1 clinical trial for BLU-285 for the treatment of patients with advanced SM, including aggressive SM (ASM), SM with associated clonal hematological non-mast cell lineage diseases (SM-AHN) and mast cell leukemia (MCL), and we are currently enrolling patients in this clinical trial. The Phase 1 clinical trial will evaluate the safety and tolerability of BLU-285 in multiple ascending doses in patients with advanced SM with the goal of establishing a maximum tolerated dose (MTD) or a recommended dose if the MTD is not achieved.

To learn more about this clinical trial, please click here.

 

BLU-554 FOR ADVANCED HEPATOCELLULAR CARCINOMA (HCC)

Our drug candidate BLU-554 is a potent and selective inhibitor of the kinase fibroblast growth factor receptor 4 (FGFR4). BLU-554 targets FGFR4 while sparing other members of the FGFR family and showing little to no inhibition of all other kinases. We estimate that up to 30 percent of patients with HCC have tumors with aberrantly activated FGFR4 signaling. HCC accounts for most liver cancers, and liver cancer is the second leading cause of cancer-related deaths worldwide. BLU-554 has shown significant anti-tumor activity including complete and sustained tumor regression in preclinical models of HCC.

We have initiated a Phase 1 clinical trial for BLU-554 for the treatment of patients with advanced HCC, and we are currently enrolling patients. The Phase 1 clinical trial will evaluate safety and tolerability of BLU-554 in multiple ascending doses in patients with advanced HCC with the goal of establishing a maximum tolerated dose (MTD) or a recommended dose if MTD is not achieved.

To learn more about this clinical trial, please click here.

BLU-667 FOR RET-ALTERED CANCERS

Our drug candidate BLU-667 is a potent and selective inhibitor of the kinase RET. RET activating fusions and mutations are key disease drivers in multiple cancers, including non-small cell lung cancer (NSCLC) and medullary thyroid cancer (MTC). RET fusions are implicated in approximately 1-2% of patients with NSCLC, and RET mutations are implicated in approximately 60% of patients with MTC. In addition, genomic analyses published by scientists at Blueprint Medicines, and others have identified RET fusions at low frequencies in colon cancer, breast cancer, and a variety of other cancers. Currently, there are no approved therapies that selectively target RET-driven cancers. Several approved multi-kinase inhibitors with RET activity are being evaluated in clinical trials in patients with RET-driven cancers. However, clinical activity has been limited, likely due to insufficient inhibition of RET and off-target toxicities. In preclinical studies using biochemical and cellular assays, and tumor models, BLU-667 was active against RET fusions and mutations, including predicted resistance mutations.

We have initiated a Phase 1 clinical trial for BLU-667 in RET, and we are currently enrolling patients. The Phase 1 clinical trial will evaluate the safety and tolerability of increasing doses of BLU-667 in patients with NSCLC, MTC, and other advanced solid tumors with the goal of establishing a maximum tolerated dose (MTD) or a lower recommended dose if appropriate. Once the MTD is reached, or a recommended dose is established, Blueprint Medicines plans to open expansion cohorts for patients with RET-altered NSCLC, patients with MTC, and patients with RET-altered solid tumors other than NSCLC and MTC.

To learn more about this clinical trial, please click here.

Last Updated: November 13, 2015