Cogent Biosciences shared its Phase II APEX clinical trial on bezuclastinib for patients with AdvSM and showed promise in treating the rare blood disorder.
In a presentation at the 2022 European Hematology Association Congress in Austria, Cogent Biosciences shared results from its Phase II APEX clinical trial on bezuclastinib, which is being developed to treat patients with advanced systemic mastocytosis (AdvSM). The drug showed promise in treating the rare blood disorder.
Bezuclastinib, a selective KIT D816V inhibitor, was tested for safety and tolerability on 11 patients. The first part of the trial is intended to determine which of the four doses - 50 mg twice a day, 100 mg twice a day, 200 mg twice a day or 400 mg daily - will be used in Part II of the study. KIT D816V is responsible for driving systemic mastocytosis, which is characterized by a proliferation of mast cells, a type of white blood cell that accumulates in the internal organs, including the bone marrow.
Around 90% of people living with systemic mastocytosis have non-advanced systemic mastocytosis, a life-long illness that manifests chronic symptoms such as bloating, vomiting, abdominal pain, diarrhea, skin lesions, urticaria pigmentosa, gastroesophageal reflux and skin flushing. People with AdvSM typically suffer from myriad debilitating symptoms, including bone fractures, ascites, anemia and internal organ enlargement. The median life expectancy for this illness is less than 3.5 years.
At the May 24 data cut-off, all 11 participants in Cogent’s study reported achieving an over 50% reduction in serum tryptase levels by central assessment. All eight patients who were C3D1 evaluable also saw their bone marrow mast cell volumes reduced by more than 50% and their KIT D816V variant allele fraction by droplet digital polymerase chain reaction decreased. Patients were treated for 0.5 to 4.8 months.
“These results reinforce the hypothesis that a potent, selective KIT D816V inhibitor with limited CNS penetration has the potential to provide meaningful clinical activity to all systemic mastocytosis patients, without the tolerability challenges seen with other available treatment options. Based on these results, we expect to accelerate our timelines and investment and look forward to providing another APEX clinical update by the end of 2022,” Andrew Robbins, the chief executive officer at Cogent Biosciences, said in a statement.
Given the positive start, Cogent said it will continue to enroll patients into Part I and will conduct an interim analysis once around 28 patients have already been given at least two cycles of treatment. The company hopes to share more in-depth results by the end of 2022.
“Advanced systemic mastocytosis is a severe, debilitating hematologic disorder and physicians and patients remain in search of more effective and better tolerated treatment options to fight this disease. If results like these can be shown in a larger set of patients with AdvSM, I believe bezuclastinib has the potential to help us take a big step forward in treating systemic mastocytosis patients,” Dr. Daniel DeAngelo, chief of the leukemia division at the Dana-Farber Cancer Institute and the APEX study’s investigator concluded.
