Ziftomenib in Relapsed or Refractory <i>NPM1</i> -Mutated AML
Abstract
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.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (50)
Florian H. Heidel
Mithun V. Shah
Mayo Clinic, Rochester, MN
Robert L. Redner
University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA
Amitava Mitra
Kura Oncology, Inc, San Diego, CA
Harris S. Soifer
Kura Oncology Inc., San Diego, California, United States
Marilyn Tabachri
Kura Oncology, Inc, San Diego, CA
Zijing Zhang
Marcie Riches
Kura Oncology Inc., San Diego, California, United States
Daniel Corum
Kura Oncology Inc., San Diego, California, United States
Mollie Leoni
Kura Oncology, Inc., Boston, Massachusetts, United States
Lionel Adès
Jessica K. Altman
Division of Hematology/Oncology Department of Medicine Robert H. Lurie Comprehensive Cancer Center Northwestern University Chicago Illinois USA
Maria R. Baer
10University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD
Suresh Balasubramanian
Karmanos Cancer Institute, Wayne State University, Detroit, MI
Frederic Barabé
Julie Bergeron
10Hopital Masionneuve-Rosemont, Montreal, Canada
Teresa Bernal del Castillo
Hospital Universitario Central de Asturias–Instituto Universitario del Principado de Asturias–Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain
Céline Berthon
29Service d’Hématologie, Centre Hospitalier Universitaire de Lille, Hôpital Claude-Huriez, Lille, France
Adolfo De La Fuente Burguera
3Department of Hematology, MD Anderson Cancer Center Madrid, Madrid, Spain
Dries Deeren
11AZ Delta Roeselare, Roeselare, Belgium
Mahmoud Elsawy
Harry Erba
28Duke University Medical Center, Durham, United States
Jordi Esteve Reyner
Amir T. Fathi
Massachusetts General Hospital Cancer Center–Harvard Medical School, Boston
Kateryna Fedorov
3Vanderbilt University Medical Center, Department of Medicine, Division of Hematology and Medical Oncology, Nashville, United States
James Foran
6Mayo Clinic Comprehensive Cancer Center, Jacksonville, United States
Caterina Giannini
Maël Heiblig
9Department of Hematology, Centre Hospitalier Universitaire de Lyon, Lyon, France
Florian Heidel
Ghayas C. Issa
Mohamad Khawandanah
Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
Francesco Lanza
1AUSL ROMAGNA, Hematology Unit & Romagna Transplant Network, Ravenna, Italy
Yazan F. Madanat
UT Southwestern Medical Center, Dallas, Texas, United States
James McCloskey
John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States
Pau Montesinos
Hospital Universitari i Politecnic La Fe, Valencia, Spain
Cristina Papayannidis
2IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy
Agustin Penedo
7START Madrid CIOCC Centro Integral Oncologico Clara Campal, Madrid, Spain
Pierre Peterlin
12Department of Hematology, Centre Hospitalier Universitaire de Nantes, Nantes, France
Kristen Pettit
11University of Michigan, Ann Arbor, United States
Arnaud Pigneux
Robert Redner
Gail J. Roboz
Weill Cornell Medicine, New York Presbyterian Hospital, New York
Eduardo Rodríguez-Arbolí
Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS/CSIC), University of Seville, Seville, Spain
Olga Salamero Garcia
Hospital Universitari Vall d'Hebron and Institute of Oncology (VHIO), Universitat Autonoma of Barcelona, Barcelona, Spain
Adrian Schwarzer
3Universitätsmedizin Greifswald, Greifswald, Germany
Mithun Shah
1Mayo Clinic, Division of Hematology, Department of Medicine, Rochester, United States
Matthew Ulrickson
28Banner MD Anderson Cancer Center, Gilbert, AZ
Adriano Venditti
23Department of Biomedicine and Prevention, University of Rome tor Vergata, Rome, Italy
Roland B. Walter
Eunice S. Wang
30Roswell Park Cancer Institute, Buffalo, NY