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ASH 2017: Rapid Responses, Few Adverse Effects Seen With Targeted Agent in Phase I Trial in Systemic Mastocytosis

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Key Points

  • BLU-285 quickly produced lasting reductions in both cellular levels of mast cells and molecular levels of the mutated gene.
  • Of 18 evaluable patients with aggressive systemic mastocytosis, 72% had an overall response, and 100% had disease control.

In a phase I trial, patients with an advanced or aggressive form of systemic mastocytosis, a rare blood disorder, had rapid and durable responses with few adverse effects following treatment with an investigational drug that targets the genetic mutation found in more than 90% of cases. Results were presented by DeAngelo et al at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 2).

The once-daily pill, BLU-285, targets a mutation in KIT D816V that is found in almost all cases of advanced systemic mastocytosis, a disease that originates in mast cells. The normal role of mast cells is to help protect the body from infection and aid in wound healing. Systemic mastocytosis occurs when mast cells start to grow uncontrollably. In its aggressive form, it spreads rapidly throughout the body, invading the liver, spleen, and organs of the gastrointestinal tract. It can also develop into a rare blood cancer, mast cell leukemia. Existing treatments for advanced systemic mastocytosis are of limited effectiveness.   

“We are seeing a high rate of rapid and durable responses—with a very low rate of adverse side effects—in patients with an advanced or aggressive form of the disease,” said lead study author Daniel J. DeAngelo, MD, PhD, Associate Professor of Medicine at Harvard Medical School and a member of the adult leukemia program at the Dana-Farber Cancer Institute. “The rapidity of the improvement is extremely dramatic.”

More on BLU-285

BLU-285 was designed specifically to block the genetic mutation that drives the growth and spread of mast cells in advanced systemic mastocytosis, Dr. DeAngelo said.

The primary objective of the phase I study was to identify the maximum tolerated dose of BLU-285. Secondary objectives were to assess the drug’s activity in the body, including anticancer activity.

In the BLU-285 dose-escalation study, the first three patients enrolled received a low dose of the study drug and were monitored for adverse effects. If no adverse events were seen, the next three patients received a higher dose, and so on. Dose escalation was stopped when adverse events were seen in 30% of the patients treated. Dosing began at 30 mg/d and increased in a stepwise fashion to 400 mg/d.

In the study, BLU-285 quickly produced lasting reductions in both cellular levels of mast cells and molecular levels of the mutated gene. Of 18 evaluable patients with aggressive systemic mastocytosis, 72% had an overall response, and 100% had disease control.

This phase I trial was designed primarily to identify a safe dose of BLU-285, not to evaluate the drug’s effectiveness. The investigators are now planning a phase II study that will assess the effectiveness of a once-daily dose of 300 mg of BLU-285 in a larger number of patients.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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