New Data Shows Positive Effects of BLU-285 in Gastrointestinal Tumors

Mathew Shanley

New Phase 1 clinical findings from a study evaluating BLU-285 in patients with advanced gastrointestinal stromal tumors (GIST) supports previous data that demonstrated the drug as exhibiting strong clinical activity and an encouraging safety profile. Blueprint Medicines Corporation is developing the therapy, a potent and highly selective KIT and PDGFRα inhibitor, as a potential treatment for this population.

GISTs are tumors of the bone or connective tissue, and are the most commonly occurring sarcoma of the gastrointestinal (GI) tract. Most arise in the stomach and small intestine, and patients are typically diagnosed between the ages of 50 and 80 years old.

116 patients had been treated with BLU-285 in the dose escalation and expansion portions of the trial as of the data cutoff date of October 11, 2017. The dose escalation portion of the study has since been completed and the maximum tolerated dose (MTD) was determined to be 400 mg once daily. The data exhibited 67% (n=77) of patients with heavily pretreated KIT-driven GIST treated with 300 to 400 mg of BLUE-285 once daily had radiographic tumor reductions, and further, data showed an objective response rate (ORR) of 17% and median progression free survival (PFS) of 11.5 months.

"The updated BLU-285 data show robust clinical activity in a broad population of patients with advanced GIST," said Michael Heinrich, M.D., Professor of Medicine at Oregon Health & Science University and an investigator on the clinical trial in a press release. "In patients with PDGFRα-driven advanced GIST, the data for BLU-285 continue to be remarkable, particularly considering these patients have no effective treatment options. Importantly, I'm also very encouraged to see radiographic tumor reductions in two-thirds of patients with heavily pretreated GIST across all common KIT genotypes, as well as prolonged progression free survival in this population. Overall, these clinical results confirm recently published preclinical data showing activity across a spectrum of disease-relevant mutations and support clinical development of BLU-285 in a broad patient population."

An estimated 80% of GIST patients have KIT-drive GIST, and most patients are diagnosed after GI bleeding is discovered, or via an incidental finding during surgery. Sometimes, though, GIST can be found after the rupture of a tumor or GI obstruction.

Blueprint intends to present the data today in an oral presentation at the Connective Tissue Oncology Society 2017 Annual Meeting in Maui, Hawaii. The company is on track to begin enrolling patients in a global, randomized Phase 3 clinical trial of BLU-285 in third-line GIST in the first half of 2018.

"We are grateful to the patients, families and investigators who have contributed to the Phase 1 clinical trial to date, and we are committed to advancing the clinical development of BLU-285 quickly and responsibly," said Andy Boral, M.D., Chief Medical Officer of Blueprint Medicines. "We continue to plan for expedited development of BLU-285 in patients with PDGFRα D842V-driven GIST, and we look forward to working with the FDA under the Breakthrough Therapy Designation program to determine the fastest path forward for BLU-285 in this population. In addition, the objective responses and prolonged progression free survival we are seeing in patients with heavily pretreated KIT-driven GIST give us increased confidence in our approach to expand development of BLU-285 in third- and second-line treatment. Overall, we believe our data-driven clinical development strategy will enable productive interactions with global regulatory authorities over the course of 2018."

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