Ziftomenib

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. 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.

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. Susceptible NPM1 mutations are defined as those that result in loss of the nucleolar localization signal and the insertion of a new nuclear export signal leading to cytoplasmic accumulation of mutant NPM1 protein that disrupts normal cell function and drives leukemogenesis through altered gene expression. Pharmacologic disruption of the menin-KMT2A protein-protein interaction by ziftomenib blocks oncogenic activity of mutant NPM1, which induces differentiation of leukemic cells as evidenced by increased expression of differentiation markers.

Select patients for treatment with KOMZIFTI based on the presence of an NPM1 mutation. 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. See Full Prescribing Information for administration instructions and dosage modifications.

None. None.

Boxed warning (differentiation syndrome): Differentiation syndrome, which can be fatal, has occurred with KOMZIFTI. Signs and symptoms may include fever, joint pain, hypotension, hypoxia, dyspnea, rapid weight gain or peripheral edema, pleural or pericardial effusions, pulmonary infiltrates, acute kidney injury, and rashes. QTc Interval Prolongation: Monitor electrocardiograms and electrolytes. Correct hypokalemia and hypomagnesemia prior to treatment. Interrupt KOMZIFTI if the QTc interval is > 500 ms. Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome QTc Interval Prolongation 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. 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.

Strong or Moderate CYP3A4 Inhibitors: Monitor more frequently for adverse reactions. Strong or Moderate CYP3A4 Inducers: Avoid concomitant use. Proton Pump Inhibitors: Avoid concomitant use. H2 Receptor Antagonists and Antacids: Avoid concomitant use. If concomitant use cannot be avoided, modify KOMZIFTI administration time. Drugs that Prolong the QTc Interval: Avoid concomitant use. If concomitant use is unavoidable, monitor patients more frequently for QTc interval prolongations.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F).