Citations 1
Ziftomenib with venetoclax and azacitidine in relapsed/refractory NPM1-mutated acute myeloid leukemia
Wang, Eunice S. , Erba, Harry P. , Zeidan, Amer M., Roboz, Gail J. , Altman, Jessica, Advani, Anjali S. , Lin, Tara L. , Strickland, Stephen A. , Juckett, Mark , Pratz, Keith W., Mangan, James K. , McMahon, Christine M. , Alsfeld, Leonard Clarkson, Murthy, Guru Subramanian Guru, Rotta, Marcello, Palmisiano, Neil, McCloskey, James, Khawandanah, Mohamad, Naqvi, Kiran, Qasrawi, Ayman , Schiller, GJ, Badar, Talha, Gojo, Ivana , Yaghmour, George , Osman, Diaa, Zhang, Hongling, Tian, Ying, Soifer, Harris S., Riches, Marcie, Corum, Daniel, Leoni, Mollie, Fathi, Amir , Juckett, Mark , Saliba, Antoine N , Madanat, Yazan , Badar, Talha , Gojo, Ivana , Fathi, Amir T , Issa, Ghayas , Wang, Eunice S. , Erba, Harry Paul , Strickland, Stephen Anthony , Roboz, Gail J , Advani, Anjali S , Lin, Tara L , Zeidan, Amer M. , Altman, Jessica K. , Pratz, Keith W. , Alsfeld, Leonard C. , Balasubramanian, Suresh , Murthy, Guru Subramanian Guru , Palmisiano, Neil , McCloskey, James, Saliba, Antoine N. , Khawandanah, Mohamad , Madanat, Yazan F. , Naqvi, Kiran , Badar, Talha , Osman, Diaa , Zhang, Hongling, Soifer, Harris S. , Riches, Marcie , Corum, Daniel, Leoni, Mollie
Blood Journal | June 2, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Ziftomenib - a potent, selective, oral menin inhibitor - is approved as monotherapy for adults with relapsed/refractory (R/R) NPM1-mutated acute myeloid leukemia (NPM1-m AML). The KOMET-007 phase 1 trial investigated clinical activity and tolerability of ziftomenib in combination with standard therapies for R/R and newly diagnosed AML. Here, we report outcomes of adults with R/R NPM1-m AML treated with ziftomenib plus venetoclax/azacitidine. In phase 1a, patients received ziftomenib 200, 400, or 600 mg once daily with standard doses of venetoclax/azacitidine. In phase 1b, ziftomenib 600 mg was selected for expansion. Sixty-seven patients were treated (27 phase 1a; 40 phase 1b). Median age was 66 years, and 55% were men. Median number of prior therapies was 1 (range 1-8); 55% received prior venetoclax and 22% had prior transplantation. Most common (≥20%) grade ≥3 treatment-emergent adverse events were leukopenia (34%), thrombocytopenia (28%), febrile neutropenia and neutropenia (25% each). Six patients developed QTc prolongation (1 ziftomenib-related; grade 1), and 2 experienced differentiation syndrome (grade 3); all events were successfully managed. In patients receiving ziftomenib 600 mg, composite complete remission (CRc) rate was 46% (22/48), with 67% (12/18) achieving central measurable residual disease (MRD) negativity (<0.01% threshold). In venetoclax-naïve and -exposed patients, CRc rates were 70% (16/23) and 24% (6/25), with MRD-negativity rates of 75% (9/12) and 50% (3/6), respectively. Median duration of response was 8.6 months, and median overall survival was not reached. The combination of ziftomenib 600 mg with venetoclax/azacitidine was well tolerated with deep and durable clinical activity in R/R NPM1-m AML. This trial was registered at www.ClinicalTrials.gov as #NCT05735184.