SUMMIT: Bezuclastinib Demonstrates Reduction in NonAdvSM Symptoms


Bezuclastinib, a targeted oral therapy, shows promise in reducing disease burden and improving symptoms by 50% or more in nonadvanced systemic mastocytosis patients, as revealed in the phase 2 SUMMIT trial data presented at ASH 2023.

Prithviraj Bose, MD | Credit: The University of Texas MD Anderson Cancer Center

Prithviraj Bose, MD
Credit: The University of Texas MD Anderson Cancer Center

New data from the phase 2 clinical trial of bezuclastinib in adults with nonadvanced systemic mastocytosis (NonAdvSM) suggests use of the targeted oral therapy reduced disease burden and improved symptoms for patients with the rare blood disorder.

Presented at the 65th American Society of Hematology (ASH) Annual Meeting, results from part 1a of the SUMMIT trial, which was sponsored by was sponsored by Cogent Biosciences, suggest use of the oral, potent, and selective type 1 tyrosine kinase inhibitor was associated with a 50% or greater reduction in markers of disease burden among all patients receiving the agent, with 63% reporting their disease symptoms eased within 12 weeks of treatment.

“The era of targeted therapy offers hope, not just for alleviating symptoms but for getting to the root of the condition,” said principal investigator Prithviraj Bose, MD, professor of Leukemia at the University of Texas MD Anderson Cancer Center. “Bezuclastinib provides precision targeting without the typical central nervous system or bleeding side effects often associated with similar drugs."

A rare disease characterized by the buildup of malignant gastrointestinal cells in bone marrow and other tissues, NonAdvSM accounts for approximately 95% of the 33,000 cases of systemic mastocytosis in the US. A phase 2 multicenter, randomized, double-blind, placebo-controlled, 3-part clinical trial, SUMMIT was launched to investigate the effects of bezuclastinib in patients with NonAdvSM who have inadequate control of symptoms despite treatment with best supportive care.

For part 1a of the trial, which was the data presented at ASH 2023, trial protocol dictated patients to be randomized in a 1:1:1 ratio to 1 of 2 doses of bezuclastinib (100 or 200 mg once daily) or placebo. Of note, all patients continued to receive their baseline anti-mediator treatments throughout the trial. In part 1a of the trial, investigators planned to assess the effect of bezuclastinib on symptoms and health-related quality of life. With this in mind, patient-reported outcome measures, including mastocytosis activity score and mastocytosis quality of life, were used as outcomes of interest for the trial.

This cohort had a median age of 50 years, 75% were female, 75% of patients had the KIT D816V mutation, and all patients had an Eastern Cooperative Oncology Group Performance Status of 0-1 (90%) or 2 (10%). At baseline, patients utilized a median of 3 (range, 2 to 7) best supportive care medications, with 100% using H1 blockers, 95% using H2 blockers, and 40% using leukotriene receptor antagonists. In a baseline assessment, investigators found a majority of patients self-reported severe disease with a median mastocytosis activity score of 43 (range 22-79) and a self-reported mean score of 56 (Standard Deviation, 19) on the mastocytosis quality of life, which indicates moderate impact to health-related quality of life.

Upon analysis, a median reduction in symptoms of 48.5% was observed in patients who received the 100 mg dose of bezuclastinib. In contrast, none of the patients among the placebo arm of the trial reported significant improvement in their overall symptoms. After transitioning to bezuclastinib, 67% reported an improvement in their symptoms after 4 weeks. Further analysis indicated greater improvements in dermatological symptoms (78%), gastrointestinal symptoms (33%), and cognitive symptoms (33%) were observed at 20 weeks than at the 12-week mark.

When assessing the safety, results suggested the adverse events in the trial generally were mild and reversible, with the most frequent being a change in hair color, nausea, and peripheral edema. Investigators also pointed out there were no serious adverse events related bezuclastinib among the 100 or 200 mg cohorts.

"This drug may offer great promise in the treatment of non-advanced systemic mastocytosis," Bose added. "As we move forward, our aspiration is to optimize the dosage while maintaining a robust safety profile.”


  1. Bose P, Oh ST, Modena B, et al. Initial Results from Summit: An Ongoing, 3-Part, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of Bezuclastinib in Adult Patients with Nonadvanced Systemic Mastocytosis (NonAdvSM). Presented at: 65th American Society of Hematology (ASH) Annual Meeting. December 9-12, 2023. San Diego, CA.
  2. Mesa RA, Sullivan EM, Dubinski D, et al. Perceptions of patient disease burden and management approaches in systemic mastocytosis: Results of the TouchStone Healthcare Provider Survey. Cancer. 2022;128(20):3700-3708. doi:10.1002/cncr.34421
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