On April 24, 2026 Kyowa Kirin Co., Ltd. (TSE: 4151, "Kyowa Kirin") and Kura Oncology, Inc. (Nasdaq: KURA, "Kura") reported the first patient has been dosed in a Japanese Phase 2 registrational clinical trial (jRCT2031250550) studying ziftomenib, an oral menin inhibitor, for the treatment of relapsed or refractory (R/R) NPM1-mutated (NPM1-m) acute myeloid leukemia (AML). NPM1-m AML accounts for approximately 30% of AML patients. The initiation of this trial represents a significant step forward toward establishing a potential new treatment option for patients in Japan. Following completion of this clinical trial, Kyowa Kirin plans to file for regulatory approval in Japan.
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Ziftomenib was approved by the U.S. Food and Drug Administration (FDA) in November 2025 for the treatment of adult patients with R/R NPM1-m AML who have no satisfactory alternative treatment options, under the brand name KOMZIFTI.
"Patients with R/R NPM1-m AML often face limitations with existing treatment options and have a critical need for new therapeutic alternatives. Ziftomenib has the potential to provide a new treatment approach for these patients," said Yoshifumi Torii, Ph.D., Chief Medical Officer of Kyowa Kirin. "The initiation of this trial is part of Kyowa Kirin’s patient-centered drug development efforts in our priority area of ‘hematologic malignancies and refractory hematologic disorders.’ We will appropriately advance this trial and work diligently to confirm efficacy and safety, with the goal of ultimately providing a new treatment option to help address unmet needs for patients in Japan as soon as possible."
The trial initiated by Kyowa Kirin is a multicenter, single-arm, open-label Japanese Phase 2 clinical trial evaluating the efficacy and safety of ziftomenib in adult patients with R/R NPM1-m AML. As the primary endpoint, the trial will assess a composite complete remission rate consisting of complete remission (CR) and complete remission with partial hematologic recovery (CRh).
"The initiation of the Phase 2 clinical trial of ziftomenib in Japan represents a significant milestone in our global development strategy," said Mollie Leoni, M.D., Chief Medical Officer at Kura Oncology. "In R/R NPM1-m AML, therapeutic options remain limited in many regions and patient populations, highlighting the urgent need for innovative therapies. In clinical trials outside of Japan, ziftomenib has consistently shown a favorable efficacy and safety profile combined with the convenience of once-daily oral administration. Advancing clinical development in Japan is a meaningful step toward establishing global access to this promising therapy. We look forward to close collaboration with Kyowa Kirin to support the trial and deliver new hope to patients in need."
Kyowa Kirin Co., Ltd. is committed to the research and development of innovative medicines in areas of high unmet medical need. Ziftomenib is in development in combination with standard-of-care and targeted therapies for the front-line treatment of AML harboring NPM1 mutations, KMT2A translocations and FLT3 mutations, with the potential to benefit a broad spectrum of patients earlier in their disease course.
NPM1, nucleophosmin 1, KMT2A, lysine methyltransferase 2A, FLT3, Fms-like tyrosine kinase 3
U.S. KOMZIFTI (ziftomenib) Indication
KOMZIFTI is an oral menin inhibitor approved for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation who have no satisfactory alternative treatment options.
IMPORTANT SAFETY INFORMATION FOR KOMZIFTI FROM THE U.S. PRESCRIBING INFORMATION
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. If differentiation syndrome is suspected, interrupt KOMZIFTI, and initiate oral or intravenous corticosteroids with hemodynamic and laboratory monitoring until symptom resolution; resume KOMZIFTI upon symptom improvement.
WARNINGS AND PRECAUTIONS
Differentiation Syndrome
KOMZIFTI can cause fatal or life-threatening differentiation syndrome (DS). DS is associated with rapid proliferation and differentiation of myeloid cells. Symptoms of DS, 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, DS occurred in 29 (26%) of 112 patients with R/R AML with an NPM1 mutation who were treated with KOMZIFTI at the recommended dosage. DS 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, DS occurred in 25% of patients. Four fatal cases of DS occurred out of 39 patients with KMT2A-rearranged AML treated with KOMZIFTI. KOMZIFTI is not approved for use in patients with KMT2A-rearranged AML.
In the 112 patients with an NPM1 mutation, DS was observed with and without concomitant hyperleukocytosis, in as early as 3 days and up to 46 days after KOMZIFTI initiation. The median time to onset was 15 days. Two patients experienced more than one DS event. Treatment was interrupted and resumed in 15 (13%) patients, while it was permanently discontinued in 2 (2%) patients.
Prior to starting treatment with KOMZIFTI, reduce the WBC counts to less than 25 x 10⁹/L. If DS is suspected, interrupt KOMZIFTI, initiate oral or intravenous corticosteroids (e.g., dexamethasone 10 mg every 12 hours) for a minimum of 3 days with hemodynamic and laboratory monitoring. Resume treatment with KOMZIFTI at the same dose level when signs and symptoms improve and are Grade 2 or lower. Taper corticosteroids over a minimum of 3 days after adequate control or resolution of symptoms. Symptoms of DS may recur with premature discontinuation of corticosteroid treatment.
QTc Interval Prolongation
KOMZIFTI can cause QTc interval prolongation. In the clinical trial, QTc interval prolongation was reported as an adverse reaction in 12% of 112 patients treated with KOMZIFTI at the recommended dosage for R/R AML with an NPM1 mutation. QTc interval prolongation was Grade 3 in 8% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 9% of patients, and the increase from baseline QTcF was greater than 60 msec in 12% of patients. KOMZIFTI dose reduction was required for 1% of patients due to QTc interval prolongation. QTc prolongation occurred in 14% of the 42 patients less than 65 years of age and in 10% of the 70 patients 65 years of age or older.
Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with KOMZIFTI. Perform an ECG prior to initiation of treatment with KOMZIFTI, and do not initiate KOMZIFTI in patients with QTcF > 480 msec. Perform an ECG at least once weekly for the first four weeks on treatment, and at least monthly thereafter. Interrupt KOMZIFTI if the QTc interval is > 500 ms or the change from baseline is > 60 ms (Grade 3). In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use of KOMZIFTI with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation, result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including Torsades de Pointes, other serious arrhythmias, and sudden death.
Embryo-Fetal Toxicity
Based on findings in animals and its mechanism of action, KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 3 months after the last dose.
ADVERSE REACTIONS
Fatal adverse reactions occurred in 4 (4%) patients who received KOMZIFTI, including 2 with differentiation syndrome, 1 with infection, and 1 with sudden death. Serious adverse reactions were reported in 79% of patients who received KOMZIFTI. Serious adverse reactions occurring in ≥ 5% of patients included infection without an identified pathogen (29%), febrile neutropenia (18%), bacterial infection (16%), differentiation syndrome (16%), and dyspnea (6%).
Dosage interruption of KOMZIFTI due to an adverse reaction occurred in 54% of patients. Adverse reactions that required dose interruption in ≥ 2% of patients included infection without an identified pathogen (15%), differentiation syndrome (13%), febrile neutropenia (5%), pyrexia (4%), electrocardiogram QT prolonged (4%), leukocytosis (4%), bacterial infection (3%), cardiac failure (2%), cholecystitis (2%), diarrhea (2%), pruritus (2%), and thrombosis (2%). Dose reduction of KOMZIFTI due to an adverse reaction occurred in 4% of patients. Permanent discontinuation of KOMZIFTI due to an adverse reaction occurred in 21% of patients. Adverse reactions that required permanent discontinuation of KOMZIFTI in ≥ 2% of patients were infection without an identified pathogen (8%), bacterial infection (4%), cardiac arrest (2%), and differentiation syndrome (2%).
Most common (≥ 20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased (53%), infection without an identified pathogen (52%), potassium decreased (52%), albumin decreased (51%), alanine aminotransferase increased (50%), sodium decreased (49%), creatinine increased (45%), alkaline phosphatase increased (41%), hemorrhage (38%), diarrhea (36%), nausea (35%), fatigue (34%), edema (30%), bacterial infection (28%), musculoskeletal pain (28%), bilirubin increased (27%), potassium increased (26%), differentiation syndrome (26%), pruritus (23%), febrile neutropenia (22%), and transaminases increased (21%).
DRUG INTERACTIONS
Drug interactions may occur when KOMZIFTI is concomitantly used with:
Strong or Moderate CYP3A4 Inhibitors: Monitor patients more frequently for KOMZIFTI-associated adverse reactions.
Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of KOMZIFTI.
Gastric Acid Reducing Agents: Avoid concomitant use of KOMZIFTI with proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), or locally acting antacids. If concomitant use with H2RAs or locally acting antacids cannot be avoided, modify KOMZIFTI administration time.
Take KOMZIFTI 2 hours before or 10 hours after administration of an H2 receptor antagonist.
Take KOMZIFTI 2 hours before or 2 hours after administration of a locally acting antacid.
Drugs that Prolong the QTc Interval: Avoid concomitant use of KOMZIFTI. If concomitant use cannot be avoided, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Interrupt KOMZIFTI if the QTc interval is > 500 ms or the change from baseline is > 60 ms.
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on findings in animals and its mechanism of action, KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to starting KOMZIFTI.
Lactation: Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with KOMZIFTI and for 2 weeks after the last dose.
Infertility: Based on findings in animals, KOMZIFTI may impair fertility in females and males of reproductive potential.
Please see full Prescribing Information, including Boxed WARNING.
(Press release, Kyowa Hakko Kirin, APR 24, 2026, View Source [SID1234664755])