Updated Research Shows the Benefits of Triplet Therapy for People with NPM1 AML

New results from the phase 1 KOMET-007 clinical trial show that a triplet therapy to treat acute myeloid leukemia (AML) provides meaningful long-lasting results for people with NPM1-mutated AML. . 

What is NPM1-mutated AML?

AML is a type of blood cancer that starts in the bone marrow. The American Cancer Society estimates that around 22,720 new cases of AML will be diagnosed in the United States in 2026. NPM1 is a gene that supports the development of a protein responsible for DNA repair and regulating cell function. Changes in the NPM1 gene can lead to an uncontrolled growth of white blood cells. NPM1 Mutations are present in about 30% to 40% of adult AML cases and 2% to 8% of childhood AML cases.   

The standard treatments for AML are chemotherapy combined with a targeted therapy and sometimes a stem cell transplant. The KOMET-007 study evaluated a triplet therapy for people with relapsed or refractory NPM1-mutated AML. The therapy included ziftomenib (Komzifti) in combination with venetoclax (Venclexta) and azacitidine. The combination of venetoclax and azacitidine is sometimes known as aza-ven. 

Ziftomenib is the first once-daily targeted therapy for people with relapsed or refractory AML who have an NPM1 mutation. Azacitidine is a nucleoside metabolic inhibitor that helps control disease and improve blood counts. Venetoclax is a targeted therapy known as a BCL-2 inhibitor that works by blocking the function of the protein that helps cancer cells to survive. 

Recent research presented at the 2025 American Society of Hematology (ASH) conference highlighted the benefits in outcomes for people with AML who received aza-ven. The study showed that people with relapsed or refractory NPM1 AML had better event-free survival and overall response rate. Research also found that people who received the combination were more likely to move on to a stem-cell transplant. 

What did the KOMET-007 show?

The KOMET-007 clinical trial found that about two-thirds of patients tolerated the combination of ziftomenib and aza-ven well and had a durable response.  

For people who had not received venetoclax before, after receiving the triplet therapy, 70% achieved a composite complete remission, and 75% of patients reached measurable residual disease (MRD) negativity. These findings suggest deep responses to treatment. Responses were also seen quickly, with a median time to remission of just under four weeks.

The combination showed activity in patients who had previously received venetoclax.  However, response rates were lower in this group. Researchers also reported that the triplet therapy was generally tolerated well with low rates of differentiation syndrome and manageable side effects. 

What this means for people with NPM1-mutated AML

These findings support continued study of ziftomenib-based combinations as a potential treatment option for people with relapsed or refractory NPM1-mutated AML. 

Follow the link below to read the publication. 

Read the Full Article in Blood

You can get the latest AML news just like this delivered straight to your inbox when you subscribe to HealthTree’s AML newsletter. 

Subscribe to the AML Newsletter

Sources: 

• Kura Oncology Press Release 
  
• HealthTree-U.S. FDA Approves Ziftomenib for Relapsed/Refractory AML 
  
• HealthTree-Aza-Ven 
  
• HealthTree-Venetoclax and Azacitidine for AML: Better Responses and Fewer Complications 
  
• HealthTree-Azacitidine
• HealthTree Venetoclax