Kura Oncology and Kyowa Kirin to Present Updated Frontline Ziftomenib / 7+3 Combination Data at EHA 2026 Congress

Kura Oncology Presents Strong Frontline Ziftomenib Data at EHA 2026

Kura Oncology and Kyowa Kirin announced updated results from the Phase 1 KOMET-007 trial, evaluating ziftomenib in combination with cytarabine plus daunorubicin (7+3) for newly diagnosed NPM1-mutant (NPM1-m) or KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML). The data, to be presented at the EHA 2026 Congress, showed high composite complete response (CRc) rates of 96% for NPM1-m and 90% for KMT2A-r AML in 99 patients. Deep molecular responses were observed with MRD-negativity rates of 83% for NPM1-m and 82% for KMT2A-r. Encouraging durability was noted, with median duration of CRc not reached in NPM1-m patients at ~15 months follow-up, supporting ziftomenib's potential as a foundational frontline AML therapy.

• The KOMET-007 trial demonstrated exceptional composite complete response (CRc) rates in newly diagnosed AML patients. Specifically, 96% (47/49) of NPM1-mutant patients and 90% (45/50) of KMT2A-rearranged patients achieved CRc when treated with ziftomenib in combination with 7+3 chemotherapy. These results represent one of the largest datasets for a menin inhibitor in frontline AML, highlighting the regimen's broad efficacy across genetically defined subsets.
• Beyond high CRc rates, the study reported deep molecular responses, with measurable residual disease (MRD)-negativity rates of 83% for NPM1-mutant and 82% for KMT2A-rearranged AML among CRc responders. Durability was also encouraging, with the median duration of CRc not reached in NPM1-mutant patients at a median follow-up of 14.9 months, and 11.2 months in KMT2A-rearranged patients, suggesting sustained therapeutic benefit.
• Ziftomenib in combination with 7+3 maintained a consistent and manageable safety profile across both molecular subtypes, with no new safety signals observed with long-term treatment. These robust Phase 1 results support the ongoing Phase 3 KOMET-017 registrational program, which is currently enrolling patients and holds potential for accelerated FDA review in 2028, positioning ziftomenib as a potential foundational therapy for frontline AML.

Ziftomenib + 7+3: High Response and Durability in Frontline AML

Recent clinical investigations in acute myeloid leukemia have demonstrated promising therapeutic advances across multiple treatment modalities. The multicenter retrospective study from 13 Turkish academic centers evaluated midostaurin combined with intensive chemotherapy (3+7) in newly diagnosed FLT3-mutated AML patients, achieving an overall response rate of 87.7% and complete remission rate of 84.2%. The median overall survival reached 21.4 months, with 52.6% of patients proceeding to allogeneic stem cell transplantation in first remission. Treatment discontinuation due to intolerance or toxicity remained low at 3.5%, supporting the acceptable tolerability profile of this combination in routine clinical practice.

Target trial emulation studies using propensity score matching have provided robust evidence for venetoclax plus hypomethylating agents in elderly AML patients ≥60 years old, demonstrating superior overall survival compared to hypomethylating agents alone. This survival advantage was particularly prominent among patients ≥75 years old, with the combination also significantly reducing transfusion requirements. Additionally, the CLAD-LDAC-venetoclax regimen implemented at American University of Beirut Medical Center showed notable efficacy in frontline patients (median age 67 years), with an 88% overall response rate, 76% complete remission rate, and median overall survival of 35.3 months, though infection rates increased, especially in secondary AML patients.

The phase I dose-escalation study of bortezomib, sorafenib, and decitabine enrolled 15 patients (11 newly diagnosed, 4 relapsed/refractory AML) and achieved a 33.3% overall response rate with clinical responses observed in both patient populations. The most frequent grade ≥3 adverse events were hypertension and febrile neutropenia, while the sequential treatment approach demonstrated acceptable safety and feasibility. Emerging therapeutic strategies including menin inhibitors (revumenib and ziftomenib) have shown significant activity in NPM1-mutated and KMT2A-rearranged AML, while CAR-T cell therapies continue to face challenges with high toxicity rates and low response rates, prompting the development of consensus criteria to improve research quality and enable cross-trial comparisons.

KOMET-007 Design and the Path to Phase 3 KOMET-017

Recent clinical trials in acute myeloid leukemia have employed diverse study designs ranging from phase I dose-escalation studies to large meta-analyses, each targeting specific therapeutic questions and patient populations. These studies have utilized both prospective randomized controlled designs and retrospective cohort analyses to evaluate novel treatment approaches, prognostic biomarkers, and outcome predictors across different AML subtypes and risk categories.

Ziftomenib's Frontline Potential Reshapes AML Induction

The latest data from the KOMET-007 trial marks a potentially transformative moment for the treatment of acute myeloid leukemia (AML) driven by NPM1 mutations (NPM1-m) or KMT2A rearrangements (KMT2A-r). These genetic subtypes are notoriously aggressive, often leading to poor prognoses and high relapse rates even with intensive chemotherapy. The impressive composite complete response rates of 96% for NPM1-m and 90% for KMT2A-r AML, achieved when ziftomenib is combined with standard 7+3 induction chemotherapy in newly diagnosed patients, suggest a significant leap forward. Furthermore, the high rates of measurable residual disease (MRD) negativity, exceeding 80% in both groups, indicate deep molecular responses that are crucial for sustained remission and improved long-term outcomes.

This strong performance in the frontline setting positions ziftomenib to potentially redefine the standard of care for these patient populations. While menin inhibitors like ziftomenib have already demonstrated efficacy in the relapsed/refractory setting, their integration into initial induction therapy could prevent the genomic and epigenomic evolution that often leads to upfront resistance in later lines of treatment. However, the path forward is not without its challenges. Differentiation syndrome, a known adverse event associated with menin inhibitors, requires vigilant management, particularly given its higher incidence in KMT2A-r patients. Moreover, the emergence of acquired resistance, often driven by specific MEN1 mutations, remains a critical consideration for long-term efficacy. While ziftomenib shows activity against some resistance mutations, others may necessitate sequential therapies or novel combination strategies. The competitive landscape, with other menin inhibitors already approved or in advanced development, also underscores the need for continued robust clinical evidence to solidify ziftomenib's unique value proposition. Ultimately, these results reinforce the growing optimism that targeted therapies, when strategically combined with established regimens, can fundamentally alter the trajectory of historically difficult-to-treat leukemias.