Clinical Activity is Induced by Ziftomenib in NPM1-mutant R/R AML

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Clinical Activity Is Induced by Ziftomenib in NPM1-mutant R/R AM

Source – Kura Oncology

Phase I data from the KOMET-001 trial (NCT04067336) showed that treatment with Ziftomenib, a menin-MLL (KMT2A) inhibitor, appeared to be safe and effective in treating patients with NPM1-mutated, relapsed/refractory acute myeloid leukemia (AML) who had undergone extensive pretreatment and who also had co-mutations.

Nineteen patients (95%) had diarrhea (n = 9; 45%), hypokalemia (n = 8; 40%), nausea (n = 6; 30%), anemia (n = 6; 30%), back pain (n = 6; 30%), and epistaxis (n = 5; 25%). Treatment-emergent adverse events (TEAEs) of any grade also occurred in 19 patients (95%). A grade 3 or higher TEAE was encountered by 17 individuals (85%), including anemia (25%) and thrombocytopenia (20%).

Additionally, nausea (20%) and differentiation syndrome (20%) were two other treatment-related adverse events (TRAEs) that 12 patients (60%) reported experiencing. Six patients (30%) developed TRAEs of grade 3 or above.

“We are aware that differentiation syndrome is a side effect of special relevance for this class of drugs. There was just one report of a grade 3 differentiation syndrome among these 20 individuals. Specific case was successfully managed with the use of appropriate mitigation, including steroids. He also noted that there were no reports of drug-induced QTc prolongation.”

“I would also like to note that a patient with complete remission and incomplete hematologic recovery went to transplant and is currently in remission following stem cell transplant. The patients with (morphologic leukemia-free state), unfortunately, prior to achieving count recovery, died from complications of COVID infection.”

Amir Fathi, MD, associate professor of medicine at Harvard Medical School and programme director of the Centre for Leukaemia at Massachusetts General Hospital

The average time it took for Ziftomenib to start working was 51 days (the range was 26–225).

The swim plot shows that the continuing duration of response (DOR) for one patient with a CR at the 200-mg dosage is 36 cycles. For those who had CRc, the median DOR was 8.2 months.

Two patients eventually underwent stem cell transplants, with one remaining in CR and the other receiving Ziftomenib for post-stem cell transplant maintenance.

Six patients (67%) who attained CRc had four MRD-negative individuals.

In principle, then, we believe that this drug still has efficacy against a number of these resistance mutations, according to Fahti.

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