Microscopic view of blood cells showing leukemia, highlighting Ziftomenib Plus induction for AML treatment.
Articles / Hematology 06/24/2026

EHA 2026: Ziftomenib Plus Intensive Induction Shows Deep Durable Responses in Newly Diagnosed NPM1-Mutant or KMT2A-Rearranged AML

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Key Points

  • In the phase 1b portion of KOMET-007, ziftomenib plus standard 7+3 induction yielded composite complete remission (CRc) rates of 96% in NPM1-mutant (n = 49) and 90% in KMT2A-rearranged (n = 50) newly diagnosed acute myeloid leukemia (AML), with local minimal residual disease (MRD) negativity rates of 83% and 82%, respectively.
  • Responses were highly durable (median CRc duration not reached in NPM1-mutant at a median follow-up of 14.9 months) with encouraging 1-year overall survival (OS) rates of 94% (NPM1-mutant) and 70% (KMT2A-rearranged).
  • The safety profile was consistent with intensive chemotherapy, with low additive myelosuppression and manageable on-target effects.
  • These results support the ongoing phase 3 KOMET-017 registrational trial evaluating ziftomenib with intensive or nonintensive backbones in frontline NPM1-mutant or KMT2A-rearranged AML.

Ziftomenib, a potent, selective oral menin inhibitor, continues to build momentum across the AML spectrum. Already FDA-approved as monotherapy for relapsed/refractory NPM1-mutant AML, updated frontline combination data presented at the 2026 European Hematology Association (EHA) Congress highlight its potential to improve outcomes when added to standard intensive induction.

KOMET-007 Trial Overview

KOMET-007 (NCT05735184) is an ongoing multicohort, open-label phase 1a/b study evaluating ziftomenib combined with intensive induction (7+3) in NPM1-mutant or KMT2A-rearranged AML. The trial reported safety and efficacy for patients with newly diagnosed disease treated with ziftomenib 600 mg once daily starting on Day 8 of induction plus cytarabine/daunorubicin (7+3), continued through consolidation and maintenance.

The trial enrolled adults aged 18 years or older who were newly diagnosed with NPM1-mutant or KMT2A-rearranged AML. Primary end points included adverse events (AEs) and CR. Key secondary end points were CRc, overall response rate, duration of response, and OS.

Efficacy Highlights

  • CRc Rates: 96% (47/49) in NPM1-mutant and 90% (45/50) in KMT2A-rearranged.
  • MRD Negativity (local assessment among CRc responders): 83% (39/47) NPM1-mutant and 82% (32/39) KMT2A-rearranged. In the NPM1-mutant group, 92% (36/39) achieved MRD negativity by 20 weeks.
  • Durability: Median CRc duration not reached in NPM1-mutant; 11.2 months in KMT2A-rearranged.
  • Survival: Median OS not reached; 1-year OS rates 94% (NPM1-mutant) and 70% (KMT2A-rearranged).

At data cutoff, 94% of patients with NPM1-mutant disease and 62% of KMT2A-rearranged patients remained on the study. 

Safety Profile

The most common grade 3 or greater treatment-emergent AEs were (≥20% overall, similar across cohorts): febrile neutropenia (64%), thrombocytopenia (57%), anemia (36%), neutropenia (28%), and leukopenia (27%). Investigator-assessed grade 3 or greater ziftomenib-related AEs occurred in 54% of patients, most commonly thrombocytopenia (21%), anemia (15%), neutropenia (13%), febrile neutropenia (13%), and pruritus (10%).

  • Differentiation Syndrome: Grade 3 in 3 patients (all KMT2A-rearranged; ziftomenib-related); all resolved with protocol-specified mitigation (no grade 4).
  • QTc Prolongation: Grade 3 in 4 patients (1 NPM1-mutant, 3 KMT2A-rearranged, 1 ziftomenib-related); all resolved (no grade 4).
  • Hematologic Recovery: Median time to neutrophil (≥1 × 10⁹/L) and platelet (≥100 × 10⁹/L) recovery was 29 and 28 days.

Clinical Implications of KOMET-007

The long-term KOMET-007 data demonstrate that adding ziftomenib to 7+3 delivers exceptionally durable responses with a manageable safety profile in molecularly defined, newly diagnosed AML. This reinforces the value of prompt molecular profiling for NPM1 and KMT2A alterations and highlights practical management strategies for menin inhibitor-associated AEs such as differentiation syndrome. The data provide strong rationale for the ongoing phase 3 KOMET-017 trial (NCT07007312), which will further define the role of ziftomenib combinations in frontline settings and potentially expand options for both fit and unfit patients.

Reference

Zeidan AM, Wang E, Erba HP, et al. Ziftomenib combined with intensive induction (7+3) for newly diagnosed NPM1-m or KMT2A-r acute myeloid leukemia (AML): long-term results from the KOMET-007 trial. Presented at: 2026 European Hematology Association (EHA) Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S130.