A new clinical trial evaluating the safety and efficacy of CGT9486 compared to placebo in patients with indolent or smoldering systemic mastocytosis is now recruiting participants in the US. 

The multipart, randomized, double-blind, placebo-controlled phase 2 study aims to recruit 138 adult patients with nonadvanced systemic mastocytosis—including indolent and smoldering disease—whose symptoms cannot be controlled adequately with best supportive care.

The study will be conducted in 3 parts. In the first, patients will be randomly assigned to receive 1 of 3 dose levels of CGT9486 or placebo plus best supportive care. Then a dose will be selected and used in part 2 of the trial. In part 3, all patients who completed part 1 or 2 will receive CGT9486 plus best supportive care.

The primary outcome measure will be the proportion of responders based on a reduction in a disease-specific patient-reported outcome. Secondary outcome measures will include the safety and tolerability of the treatment as assessed by the number of adverse events, and the change and percent change in patient-reported outcome measures, serum tryptase, and bone marrow mast cells. Other secondary outcome measures will include the mean change in the Mast Cell Quality of Life (MC-QOL) score, 12-item Short-Form Health Survey (SF-12), and EuroQol 5 Dimensions 5 Levels (EQ 5D-5L).

Read more about systemic mastocytosis.

The trial, sponsored by Cogent Biosciences, Inc., opened in April 2022 and is expected to be completed in November 2026.

CGT9486, also known as bezuclastinib, targets exon 17 mutations found within the KIT receptor tyrosine kinase, including KIT D816V, which remains in a constant “on” state, causing mast cells to accumulate in bone marrow and other organs and resulting in systemic mastocytosis.

CGT9486 is also in clinical trials for the potential treatment of advanced systemic mastocytosis and gastrointestinal stromal tumors, another disease associated with KIT exon 17 mutations. 

Reference

(Summit) a study to evaluate the efficacy and safety of CGT9486 versus placebo in patients with indolent or smoldering systemic mastocytosis. US National Library of Medicine. Last updated April 18, 2022. Accessed May 5, 2022.