On June 2, 2025 Kura Oncology, Inc. (Nasdaq: KURA, "Kura") and Kyowa Kirin Co., Ltd. (TSE: 4151, "Kyowa Kirin") reported the presentation of positive pivotal results from the KOMET-001 Phase 2 registration-directed trial of ziftomenib, a once-daily, oral investigational menin inhibitor, in patients with relapsed/refractory (R/R) NPM1-mutant (NPM1-m) acute myeloid leukemia (AML) in an oral session today at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, IL from May 30 – June 3, 2025 (Press release, Kura Oncology, JUN 2, 2025, View Source [SID1234653614]).
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"We are delighted to announce positive pivotal data from the KOMET-001 trial in R/R NPM1-mutated AML patients treated with ziftomenib," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "NPM1 mutations are among the most common in AML, representing approximately 30% of cases, and there are no FDA-approved therapies specifically for this patient population. With these encouraging results and a PDUFA target action date of November 30, 2025, we and our partners at Kyowa Kirin look forward to supporting FDA with its review of the ziftomenib New Drug Application (NDA) and are well-positioned to meaningfully impact relapsed or refractory patients with NPM1 mutations."
"Relapsed or refractory NPM1-mutated AML is a highly challenging disease with a poor prognosis and an urgent need for new treatments," said Eunice Wang, M.D., Chief of Leukemia Service, Professor of Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY. "The promising results for ziftomenib in this heavily pretreated population are highly encouraging. Notably, the clinically meaningful minimal residual disease (MRD)-negative responses observed as well as the similar response rates seen regardless of prior therapies, including hematopoietic stem cell transplantation (HSCT) and venetoclax, hold great promise for the potential use of ziftomenib in patients with relapsed and refractory NPM1-mutated AML."
The KOMET-001 Phase 2 population included 92 adult patients with R/R NPM1-m AML. The median age was 69 (range: 33 to 84). Patients were heavily pretreated, with 33% having received three or more prior lines of therapy (median prior lines: 2) and 59% having been previously treated with venetoclax.
A complete remission (CR) plus CR with partial hematological recovery (CRh) rate of 23% (21/92) was observed among patients with R/R NPM1-m AML in the Phase 2 portion of the KOMET-001 trial. Among those 21 patients who achieved CR/CRh, 13 had a CR and 8 had a CRh. The median duration of CR/CRh responses was 3.7 months (95% CI: 1.9, not estimable (NE)) and the restricted mean duration of response was 4.3 months (95% CI: 3.1, 5.6) at the time of the data cutoff. MRD status was assessed in 19 of 21 patients who achieved CR/CRh, and 63% (12/19) of these patients were MRD-negative.
Comparable CR/CRh rates were observed across pre-specified subgroups, regardless of prior HSCT, prior venetoclax or FLT3/IDH co-mutations. Additional patient benefit beyond CR/CRh was observed with a rate of transfusion conversion of 21% (17/82; 95% CI: 13-31) and a rate of maintenance of transfusion independence of 20% (2/10; 95% CI: 3-56). A median OS of 16.4 months (95% CI, 9.6–20.4) was observed for responders (patients who achieved CR, CRh, CRi/CRp, MLFS or PR) and a median overall survival (OS) of 3.5 months (95% CI, 2.5–4.0) was observed among non-responders.
The safety population included 112 adult patients with R/R NPM1-m AML from the pooled Phase 1b and Phase 2 portions of the KOMET-001 trial. The safety profile observed with ziftomenib in this population was consistent with previously reported data. Treatment-related adverse events (TRAEs) led to treatment discontinuations in 3% of patients. TRAEs of Grade ≥3 which occurred in more than 10% of patients were limited to differentiation syndrome (DS, 13%), which was well managed by protocol-specified mitigation strategies and no Grade 4/5 treatment-related DS was observed. Although QTc prolongation (1 Gr2; 2 Gr3) was reported in three patients per investigator assessment, all three patients were on concomitant medications associated with QTc prolongation, two had electrolyte abnormalities and one had a prior diagnosis of atrial fibrillation.
"Beyond ziftomenib’s clinical activity, we are highly encouraged by its consistent safety and tolerability profile," said Mollie Leoni, MD, Chief Medical Officer of Kura Oncology. "Notably, the low rate of myelosuppression, low discontinuation rate, lack of clinically significant QTc prolongation, absence of drug-drug interactions, and effective management of differentiation syndrome underscore ziftomenib’s potentially favorable benefit-risk profile for patients with relapsed or refractory NPM1-mutated AML."
"The data presented at ASCO (Free ASCO Whitepaper) strengthen our conviction that ziftomenib has potential to become a meaningful treatment option for patients with relapsed or refractory AML with NPM1 mutations — patients who often face limited treatment options and significant uncertainty regarding their prognosis," said Takeyoshi Yamashita, Ph.D., Executive Vice President and Chief Medical Officer of Kyowa Kirin. "Encouraged by the favorable safety, tolerability, and promising clinical activity observed thus far, Kyowa Kirin, in collaboration with Kura, is working with urgency and purpose to bring ziftomenib monotherapy to patients as swiftly and responsibly as possible."
Virtual Investor Event
Kura will host a virtual investor event featuring company management and investigators from the KOMET-001 trial of ziftomenib in R/R NPM1-m AML at 7:30pm ET / 4:30pm PT on Monday, June 2, 2025. Those who would like to participate may access the live webcast here, or register in advance for the teleconference here.The event can also be accessed on the Investors section of Kura’s website at www.kuraoncology.com. An archived replay will be available shortly after the conclusion of the live event.