Ziftomenib

Ziftomenib is a menin inhibitor that blocks the interaction of menin and lysine [K]-specific methyltransferase 2A (KMT2A). Acute leukemias can be driven by mutations in NPM1 that recruit the wild-type menin-KMT2A complex to promoters of leukemogenic genes.

• KOMZIFTI is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14 )] . KOMZIFTI is a menin inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options.ICD-10: C95.90

• None. None.contraindicated

Select patients for treatment with KOMZIFTI based on the presence of an NPM1 mutation. ( 2.1 ) Recommended dosage: 600 mg orally once daily until disease progression or unacceptable toxicity. For patients without confirmed disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for a clinical response. ( 2.2 ) See Full Prescribing Information for administration instructions and dosage modifications. ( 2.3 , 2.4 , 2.5 ) 2.1 Patient Selection Select patients for the treatment of relapsed or refractory AML with KOMZIFTI based on the presence of an NPM1 mutation [see Clinical Studies ( 14 )] . An FDA-approved test for the detection of NPM1 mutations is not currently available. 2.2 Recommended Dosage The recommended dosage of KOMZIFTI is 600 mg taken orally once daily until disease progression or unacceptable toxicity. Do not start KOMZIFTI until the white blood cell (WBC) count is reduced to less than 25 x 10⁹/L. For patients without confirmed disease progression or unacceptable toxicity, treatment for a minimum of 6 months is recommended to allow time for a clinical response. 2.3 Administration Instructions Administer KOMZIFTI once daily on an empty stomach (at least 1 hour before or 2 hours after a meal) [see Clinical Pharmacology ( 12.3 )]. Administer KOMZIFTI orally at about the same time each day. Swallow capsules whole. Do not open, break, or chew the capsules. If a dose of KOMZIFTI is missed or not taken at the usual time, administer the dose as soon as possible on the same day and at least 12 hours prior to the next scheduled dose.

QTc Interval Prolongation: Monitor electrocardiograms and electrolytes. Correct hypokalemia and hypomagnesemia prior to treatment. Interrupt KOMZIFTI if the QTc interval is > 500 ms. ( 5.2 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) 5.1 Differentiation Syndrome KOMZIFTI can cause fatal or life-threatening differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells. Symptoms of differentiation syndrome, including those seen in patients treated with KOMZIFTI, may include fever, hypoxia, joint pain, hypotension, dyspnea, rapid weight gain or peripheral edema, pleural or pericardial effusions, acute kidney injury, and rashes. In the clinical trial, differentiation syndrome occurred in 29 (26%) of 112 patients with relapsed or refractory AML with an NPM1 mutation who were treated with KOMZIFTI at the recommended dosage. Differentiation syndrome was Grade 3 in 13% and fatal in two patients. In broader evaluation of all patients with any genetic form of AML treated with KOMZIFTI monotherapy in clinical trials, differentiation syndrome occurred in 25% of patients. Four fatal cases of differentiation syndrome occurred out of 39 patients with KMT2A -rearranged AML treated with KOMZIFTI. KOMZIFTI is not approved for use in patients with KMT2A -rearranged AML.

The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome [see Warnings and Precautions ( 5.1 )] QTc Interval Prolongation [see Warnings and Precautions ( 5.2 )] The most common adverse reactions (≥20%) are infection without an identified pathogen, hemorrhage, diarrhea, nausea, fatigue, edema, bacterial infection, musculoskeletal pain, differentiation syndrome, pruritus, febrile neutropenia, and transaminases increased. ( 6.1 ) The most common laboratory abnormalities (≥10%) are aspartate aminotransferase increased, potassium decreased, albumin decreased, alanine aminotransferase increased, sodium decreased, creatinine increased, alkaline phosphatase increased, bilirubin increased, potassium increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kura Oncology, Inc., at 1-844-KURAONC, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed or Refractory AML with an NPM1 Mutation The safety of KOMZIFTI for the treatment of patients with relapsed or refractory AML with an NPM1 mutation was evaluated in KO-MEN-001 [see Clinical Studies ( 14 )] . Patients received KOMZIFTI 600 mg once daily (n=112). The median duration of exposure to KOMZIFTI was 2.2 months (range 0.1 to 21.5 months).

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on KOMZIFTI use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, oral administration of ziftomenib to pregnant mice during the period of organogenesis resulted in adverse developmental outcomes, including embryo-fetal mortality, structural abnormalities, and altered fetal growth at maternal exposures approximately 0.3 times the human exposure (AUC) at the recommended dose (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Ziftomenib was administered orally twice daily to pregnant mice at doses of 6, 20, and 60 mg/kg/day during organogenesis (gestation days 6-15).

Metabolism

Ziftomenib pharmacokinetics were characterized in patients with relapsed or refractory AML. Pharmacokinetic parameters are presented as mean (% CV), unless otherwise specified.

• Nov 13, 2025NDANDA220305Kura

1. 1Death421%
2. 2Differentiation Syndrome421%
3. 3Nausea316%
4. 4Off Label Use316%
5. 5Drug Ineffective211%
6. 6Pericardial Effusion211%
7. 7Pericarditis211%
8. 8Product Use In Unapproved Indication211%
9. 9Red Blood Cell Count Decreased211%
10. 10Atrial Fibrillation15.3%
11. 11Bacterial Infection15.3%
12. 12Cardiac Disorder15.3%
13. 13Electrocardiogram Qt Prolonged15.3%
14. 14Faeces Hard15.3%
15. 15Fatigue15.3%

The 10 most recently updated of 17 ClinicalTrials.gov registrations naming Ziftomenib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Phase I Study Investigating the Combination of the Menin Inhibitor Ziftomenib With Venetoclax and Gemtuzumab in Pediatric Patients With Acute Myeloid Leukemia
  Recruiting · Phase 1 · Interventional · 22 enrolled · M.D. Anderson Cancer Center
  NCT06448013updated 2026-06-12
• TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II
  Recruiting · Phase 1 · Phase 2 · Interventional · 90 enrolled · Tanja Andrea Gruber
  NCT05848687updated 2026-06-03
• A Phase 2 Clinical Study of Ziftomenib in Patients With Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia
  Recruiting · Phase 2 · Interventional · 6 enrolled · Kyowa Kirin Co., Ltd.
  NCT07623616updated 2026-06-03
• Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML
  Recruiting · Phase 3 · Interventional · 1,300 enrolled · Kura Oncology, Inc.
  NCT07007312updated 2026-06-03
• Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 And IDH1 Co-Mutated Acute Myeloid Leukemia
  Not yet recruiting · Phase 1 · Interventional · 20 enrolled · M.D. Anderson Cancer Center
  NCT07411586updated 2026-05-15
• First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 263 enrolled · Kura Oncology, Inc.
  NCT04067336updated 2026-05-13
• A Real-world Study on the Efficacy and Safety of Menin Inhibitors as Maintenance After Allo-HSCT
  Recruiting · Observational · 20 enrolled · The First Affiliated Hospital of Soochow University
  NCT07559695updated 2026-04-30
• Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia
  Recruiting · Phase 1 · Interventional · 171 enrolled · Kura Oncology, Inc.
  NCT06001788updated 2026-04-14
• Ziftomenib Maintenance Post Allo-HCT
  Recruiting · Phase 1 · Interventional · 22 enrolled · Massachusetts General Hospital
  NCT06440135updated 2026-03-19
• A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML
  Recruiting · Phase 1 · Interventional · 420 enrolled · Kura Oncology, Inc.
  NCT05735184updated 2026-03-13

Frequently asked questions

How does Ziftomenib work?

Ziftomenib is a menin inhibitor that blocks the interaction of menin and lysine [K]-specific methyltransferase 2A (KMT2A). Acute leukemias can be driven by mutations in NPM1 that recruit the wild-type menin-KMT2A complex to promoters of leukemogenic genes.

What is Ziftomenib used for?

According to FDA labeling, Ziftomenib carries indications including: KOMZIFTI is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14 )] . KOMZIFTI is a menin inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 ( NPM1 ) mutation who have no satisfactory alternative treatment options.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ziftomenib?

Ziftomenib is classified as Menin Inhibitor, Menin Inhibitors, Cellular Proliferation Alteration, Increased Cellular Death.

What are the brand names for Ziftomenib?

Ziftomenib is marketed under brand names including Komzifti.

What are the contraindications for Ziftomenib?

Ziftomenib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.