Results from phase 2 of the SUMMIT clinical trial suggest bezuclastinib may help treat the underlying cause of nonadvanced systemic mastocytosis (SM), as well as its symptoms.
The findings will be presented at the 67th Annual Meeting of the American Society of Hematology being held December 6-9, 2025, in Orlando, Florida.
SM happens when certain immune cells, called mast cells, build up in the body and release chemicals that cause itching, flushing, stomach pain, dizziness and fatigue. Most people with this disease have a specific gene change called KIT D816V, which causes mast cells to grow and behave abnormally. Bezuclastinib is a pill designed to block that gene’s activity.
In the new study, people taking bezuclastinib not only had better symptom relief than those on placebo — they also had significantly lower levels of the faulty KIT D816V gene and fewer mast cells in their bone marrow.
Nearly nine out of 10 patients (87%) taking bezuclastinib had a 50% or greater drop in serum tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM., a key marker of mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. activity, while no one on the placebo did.
“These data support our conviction that based on bezuclastinib’s potential to fundamentally modify the disease in non-advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. patients, it has the potential to become the preferred standard of care in this patient population,” said Andrew Robbins, the president and chief executive officer of Cogent Biosciences, the company developing the treatment.
Read more about SM treatment and care
The SUMMIT clinical trial included 179 adults with nonadvanced SMNonadvanced SM In these subtypes of SM, mast cells accumulate in the body but do not usually cause severe organ damage. Nonadvanced SM includes the subtypes indolent SM and smoldering SM. who took 100 mg of bezuclastinib or a placebo (a pill with no medicine) for 24 weeks, in addition to their regular medicines.
Most side effects from bezuclastinib were mild and reversible. The most common were hair color changes, changes in sense of taste, nausea, changes in liver test results, headache and hair loss.
“The treatment was generally well-tolerated and effective across a population that is representative of the real-world non-advanced SM population, including smoldering SMSmoldering SM A subtype of nonadvanced SM, with a higher mast cell burden than the indolent subtype. Smoldering SM has a higher likelihood of progressing to an advanced form.,” the researchers concluded.
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