Hello, my name is Dr. Amir Fati. I'm a leukemia specialist at Massachusetts General Hospital in Boston, Massachusetts. I'm also an associate professor of medicine at Harvard Medical School. I specialize in acute leukemias and bone marrow cancers and conduct clinical trials in these diseases to help improve the care of patients with AML. At the meeting this year, we're presenting a number of clinical trials around the menin inhibitor Ziftaminib. I personally am presenting data on the COMET001 study, which is the clinical trial phase one, phase two that assessed Ziftaminib, the menin inhibitor, in patients with relapsed or refractory KMT2A rearranged or MPM1 mutated AML. The primary focus of the data I'm presenting, however, is on the phase one B phase two portion of the study, which focused on MPM1 mutated patients and was a registrational effort for MPM1 mutated patients receiving monotherapies of Ziftaminib for relapsed or refractory disease. The study met its primary endpoint and the composite CRH rate on the study was 23%. The overall response rate, which in addition to what I just mentioned included MLFS and partial responses and CRI was 33%. So this data is quite promising, particularly for patients who have relapsed or refractory disease with multiple prior lines of treatment. The monotherapy study demonstrated that Ziftaminib was well tolerated. There was not a significant clinically meaningful QT prolongation seen with the agent that has been seen with other menin inhibitors. There was about a 13% incidence of grade three differentiation syndrome, which is based on the mechanism of the action of the menin inhibitor and menin inhibitors basically interfere with two key proteins, the binding of menin to KMT2A, which results in a upregulation of leukemogenic factors and block and differentiation. So when you prevent that from happening using a menin inhibitor, you actually get differentiation and maturation and cells going from leukemia cells to normal cells. Unfortunately, that process in a subset of patients can be quite inflammatory and lead to what's called a differentiation syndrome. That needs to be managed very carefully because if it's severe enough, can be potentially lethal and morbid. So and the treatment of that is usually steroids and cytoreductive therapies. On this trial, although there were about 13% of patients with grade three DES, as has been seen with other menin inhibitors because it's a class effect, they were all managed well with the standard approaches for the management of differentiation syndrome. The responses that were seen on this study were seen regardless of prior exposure to venetoclax or prior bone marrow transplant. So in general, we're very pleased with the data and we already have been informed that there is a PDUFA date in November of this year and hopefully this may soon become a potentially available option targeted therapy for patients with AML.
HealthTree • July 3, 2025