In a Phase I trial, patients with an advanced or aggressive form of systemic mastocytosis (AdvSM), 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 percent of cases.

This data was presented in a press conference at the 2017 ASH annual meeting.

For more information watch our interview with Prof DeAngelo.

The once-daily pill, BLU-285, targets a mutation called KIT D816V that is found in almost all cases of AdvSM, a disease that originates in mast cells, a type of white blood cell.

“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, an associate professor of medicine at Harvard Medical School and a member of the adult leukaemia program at the Dana-Farber Cancer Institute in Boston.

“The rapidity of the improvement is extremely dramatic.”

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 percent had an overall response, and 100 percent had disease control.

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 leukaemia.

Existing treatments for AdvSM are of limited effectiveness.  

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

The primary objective of the Phase I study was to identify the “maximum tolerated dose” of BLU-285 — that is, the highest dose that could be given without unacceptable levels of adverse effects.

Secondary objectives were to assess the drug’s activity in the body, including anti-cancer activity.

In the BLU-285 dose escalation study, the first three patients enrolled receive a low dose of the study drug and were monitored for adverse effects.

If no adverse events were seen, the next three patients receive a higher dose, and so on.

Dose escalation was stopped when adverse events were seen in 30 percent of the patients treated.

Dosing began at 30 mg per day and increased in a stepwise fashion to 400 mg per day.

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.

Source: ASH 2017