Nucleophosmin-1 (NPM1) mutations occur in 30% of AML cases. “Although typically associated with favorable prognosis, the beneficial impact of NPM1 decreases with increasing age in patients treated with standard intensive chemotherapy (IC) or hypomethylating agents (HMAs).”
Younger patients with the NPM1 mutation (median age, 44 years) versus older patients (median age, 69 years) have shown a profound difference in overall survival (OS): younger patients survive an average of 10.5 years, while older patients survive an average of 1.7 years.
“Although patients with NPM1-mutated AML have high response rates to first-line therapy (the first treatment given for a disease), they often have high relapse rates and poor survival outcomes. In the relapsed or refractory setting, overall survival (the percentage of patients who are alive for a certain period of time after diagnosis or treatment initiation) at 12 months is 30%.”
Relapse of AML affects about 50% of patients who have achieved remission after their first treatment. Relapse can occur several months or several years after chemotherapy. But, a majority of relapses occur 2-3 years after initial treatment. Because of this high percentage of relapse (or refractory) disease, novel approaches to medication are needed.
Phase 2 of the KOMET-001 trial has dosed its first set of patients
This is a continuation of a trial testing the efficacy of ziftomenib (it leads to the downregulation of HOXA9 and MEIS1) for relapsed or refractory patients with the NPM1 mutation (by Kura Oncology). This Phase 2 portion will determine the safety, tolerability, and anti-leukemia activity of ziftomenib in patients with NPM1 AML.
Findings from the initial Phase 1 of this study (read about HERE and HERE) discovered a 30% complete response rate (CRR) for patients given a 600 mg dose of ziftomenib (the Menin-MLL(KMT2A) Inhibitor KO-539). 199 randomized participants (still recruiting) are enrolled in this study. Phase 2 time frame is 12 months after the end of treatment.
Ziftomenib has a high tissue penetration, leading to the continuation of this trial and the effectiveness of this medication. Ziftomenib is dosed orally, once daily, in 28-day cycles. “The dosing of the first patients in the phase 2 of Kura Oncology’s KOMET-001 trial is a significant milestone for the AML patient community, especially for those with relapsed/refractory NPM1-mutant AML, an area of unmet need for which there are currently no FDA-approved targeted therapies.“
about the author
Lisa Foster is a mom of 3 daughters, a puzzle lover, writer and HealthTree advocate. She believes in the mission of the foundation and the team that builds it forward. She calls Houston, Texas home.