Citations 1
Ziftomenib in Relapsed or Refractory NPM1 -Mutated AML
Wang, Eunice S. , Montesinos, Pau , Foran, James M. , Erba, Harry P. , Rodríguez‐Arbolí, Eduardo , Fedorov, Kateryna, Heiblig, Maël , Heidel, Florian H. , Altman, Jessica K. , Baer, Maria R. , Pettit, Kristen , Papayannidis, Cristina , Walter, Roland B. , Khawandanah, Mohamad , Garcia, Olga Salamero, Bergeron, Julie , Ulrickson, Matthew L. , Redner, Robert L. , McCloskey, James, Pigneux, Arnaud , Fuente, Adolfo de la , Mitra, Amitava , Soifer, Harris S. , Tabachri, Marilyn, Zhang, Zijing , Riches, Marcie , Corum, Daniel, Leoni, Mollie , Barabé, Frédéric , Bergeron, Julie, Castillo, Teresa Bernal del, Berthon, Céline, Elsawy, Mahmoud , Reyner, Jordi Esteve, Fedorov, Kateryna, Giannini, Caterina, Heiblig, Maël, Issa, Ghayas C., Penedo, Agustín, Garcia, Olga Salamero, Ulrickson, Matthew, Venditti, Adriano , Walter, Roland B., Wang, Eunice S., Foran, James M , Erba, Harry Paul , Peterlin, Pierre , Berthon, Céline , Walter, Roland B , Shah, Mithun V , Balasubramanian, Suresh , Khawandanah, Mohamad , Bergeron, Julie , Roboz, Gail J , Ulrickson, Matthew , Pigneux, Arnaud , de la Fuente Burguera, Adolfo , Issa, Ghayas , Fathi, Amir T , Wang, Eunice S. , Montesinos, Pau , Pettit, Kristen , Papayannidis, Cristina , Heiblig, Mael , Fedorov, Kateryna, Adès, Lionel , Shah, Meera , Garcia, Olga Salamero, Madanat, Yazan F. , Roboz, Gail J. , Castillo, Teresa Bernal del, Deeren, Dries , Esteve, Jordi , Fedorov, Kateryna, Heiblig, Maël, Issa, Ghayas C., Lanza, Francesco , Garcia, Olga Salamero, Schwarzer, Adrian , Ulrickson, Matthew, Walter, Roland B., Wang, Eunice S.
Journal of Clinical Oncology | September 25, 2025 | Volume: 43 | Issue: 31 | Pages: 3381-3390
PURPOSE Ziftomenib—a potent, highly selective, oral menin inhibitor—was well tolerated and demonstrated encouraging clinical activity as monotherapy for relapsed/refractory NPM1 -mutated ( NPM1 -m) and KMT2A -rearranged AML in the KOMET-001 phase I trial. METHODS In the registration-enabling phase II part of KOMET-001, patients with relapsed/refractory NPM1 -m AML received ziftomenib 600 mg once daily. The primary end point was the rate of complete remission with full hematologic recovery (CR)/CR with partial hematologic recovery (CRh). RESULTS From January 26, 2023, to May 13, 2024, 92 patients (median age, 69 years [range, 33-84]) were treated. The primary end point was met, with a CR/CRh rate of 22% (95% CI, 14 to 32; P = .0058); 61% were negative for measurable residual disease. Overall response rate was 33% (95% CI, 23 to 43), with a median duration of 4.6 months (95% CI, 2.8 to 7.4). Prespecified subgroup analyses showed comparable CR/CRh regardless of previous therapy, including venetoclax, or type of comutations. Median overall survival was 6.6 months (95% CI, 3.6 to 8.6). Common grade ≥3 treatment-emergent adverse events were febrile neutropenia (26%), anemia (20%), and thrombocytopenia (20%). Differentiation syndrome occurred in 25% of patients (15% grade 3; no grade 4-5) and was manageable with protocol-defined mitigation. Three patients (3%) discontinued treatment because of ziftomenib-related adverse events. CONCLUSION Ziftomenib demonstrated significant clinical benefit and deep responses in patients with heavily pretreated, relapsed/refractory NPM1 -m AML. Ziftomenib was well tolerated with a safety profile consistent with previous studies, including manageable differentiation syndrome, lack of clinically significant QTc prolongation, and low rates of myelosuppression.