FDA Approves Komzifti for NPM1-Mutated AML Based on Positive Phase I/II KOMET-001 Trial Data

The FDA has approved Komzifti (ziftomenib) for adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible NPM1 mutation who have no satisfactory alternative treatment options.¹

The approval, making Komzifti the first and only once-daily, oral menin inhibitor approved for R/R NPM1-mutated (NPM1-m) AML, is based on positive data from the KOMET-001 clinical trial (NCT04067336).

In a company statement, Troy Wilson, PhD, JD, president and CEO of Kura Oncology, said: “Komzifti combines compelling efficacy, a favorable safety profile, compatibility with concomitant medications, and convenient once-daily oral administration in a population with few effective treatment options. These features highlight Komzifti’s potential to serve as the menin inhibitor of choice in its approved indication. Together with our partner, Kyowa Kirin, we remain committed to advancing development of KOMZIFTI across the treatment continuum for AML, where its best-in-class profile offers potential for even greater impact in combination regimens and earlier lines of therapy. We are fully prepared to launch Komzifti today and deliver this new medicine to patients in need.”

Approval based on positive outcomes from KOMET-001

Kura Oncology and Kyowa Kirin presented positive findings from the KOMET-001 study in June at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. In the Phase II portion of the trial, 23% (21/92) of R/R NPM1-m AML patients saw a complete remission (CR) plus CR with partial hematological recovery (CRh).²

Further results from KOMET-001 include:

• Among 21 patients achieving CR/CRh, responses lasted a median 3.7 months, and 63% of evaluable responders were MRD-negative.
• CR/CRh rates were consistent across subgroups, and additional benefits included 21% transfusion conversion and 20% maintenance of transfusion independence.
• Median overall survival was 16.4 months for responders versus 3.5 months for non-responders.
• In 112 treated adults, pooled from the Phase Ib and Phase II portions, ziftomenib showed a safety profile aligned with prior data, with treatment-related adverse events (TRAE)-related discontinuations in 3%.
• Grade ≥3 TRAEs were mainly differentiation syndrome (13%), which was manageable, and rare QTc prolongation occurred in patients with confounding risk factors.

In the statement, Eunice Wang, MD, chief of the leukemia service and professor of oncology at Roswell Park Comprehensive Cancer Center, said: “Komzifti addresses a critical need for adult patients with R/R NPM1-m AML, many of whom are older and unable to tolerate intensive chemotherapy or transplant. The clinical data demonstrate deep and durable responses with a manageable safety profile, including no drug-drug interactions and no Boxed Warnings for QTc prolongation or Torsades de Pointes—key advantages for patients on multiple concurrent medications. This approval equips physicians with a new oral therapy to integrate into care and improve outcomes for this vulnerable patient population.”

KOMET-001 trial design

KOMET-001 is a first-in-human, open-label study which evaluated Komzifti’s safety and efficacy in 112 R/R NPM1-m AML patients. The trial features a Main Study and four sub-studies.³

• The Main Study is a Phase I/II dose-escalation and expansion trial.
• Phase Ia identifies the maximum tolerated dose and recommended Phase II dose, while Phase Ib evaluates safety, tolerability, and the minimal biologically effective dose in biomarker-defined cohorts.
• Phase II assesses safety, tolerability, and anti-leukemic activity specifically in patients with NPM1-m AML.
• Sub-study 1 and Sub-study 2 evaluate drug–drug interactions between ziftomenib and midazolam or itraconazole, respectively.
• Sub-study 3 and Sub-study 4 investigate ziftomenib’s dosing, safety, and clinical activity in KMT2A-rearranged ALL and additional R/R AML genetic subgroups.

References

1. Kura Oncology and Kyowa Kirin Announce FDA Approval of KOMZIFTI™ (ziftomenib), the First and Only Once-Daily Targeted Therapy for Adults with Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia. News release. Kura Oncology and Kyowa Kirin. November 13, 2025. Accessed November 14, 2025. https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-announce-fda-approval-komziftitm

2. Kura Oncology and Kyowa Kirin Report Positive Pivotal Ziftomenib Monotherapy Data at 2025 ASCO Annual Meeting. News release. Kura Oncology and Kyowa Kirin. June 2, 2025. Accessed November 14, 2025. https://www.globenewswire.com/news-release/2025/06/02/3092389/35186/en/Kura-Oncology-and-Kyowa-Kirin-Report-Positive-Pivotal-Ziftomenib-Monotherapy-Data-at-2025-ASCO-Annual-Meeting.html

3. First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia. ClinicalTrials.gov. Updated November 10, 2025. Accessed November 14, 2025. https://www.clinicaltrials.gov/study/NCT04067336