Kura Oncology and Kyowa Kirin Announce Positive Ziftomenib Combination Data at ASH Meeting

In a significant development for the treatment of acute myeloid leukemia (AML), Kura Oncology, Inc. and Kyowa Kirin Co., Ltd. have revealed promising results from their KOMET-007 Phase 1 study. The study investigates the effectiveness of ziftomenib, a selective oral menin inhibitor, in combination with standard treatments such as cytarabine/daunorubicin (7+3) and venetoclax/azacitidine (ven/aza) in patients with NPM1-mutant (NPM1-m) and KMT2A-rearranged (KMT2A-r) AML. These findings were shared at the 2024 American Society of Hematology (ASH) Annual Meeting.

The interim analysis from the Phase 1a portion of the KOMET-007 trial demonstrated a 100% complete remission (CR) rate in patients with NPM1-mutant AML and an 83% CR rate in those with KMT2A-rearranged AML when treated with the 7+3 combination. Additionally, 100% of NPM1-m patients and 96% of KMT2A-r patients were alive at the data cutoff, with median follow-ups of 31 and 19 weeks, respectively. The trial also showed promising clinical activity in relapsed/refractory (R/R) AML patients treated with ven/aza, including those who had previous exposure to venetoclax. Ziftomenib was generally well tolerated across all dose levels in combination with standard care treatments.

In the 7+3 combination cohorts, on-target differentiation syndrome (DS) occurred in 2% of patients, while 8% of patients in the ven/aza combination cohorts experienced on-target DS. Grade 3 or higher treatment emergent adverse events occurring in at least 20% of patients included febrile neutropenia, decreased platelet count, anemia, and neutropenia. However, all instances of DS were manageable, and no patients discontinued due to DS.

The Phase 1b expansion portion of KOMET-007 is currently enrolling patients at a 600 mg dose level in all cohorts, including those with newly diagnosed NPM1-m or KMT2A-r AML in combination with ven/aza. Among the response-evaluable patients in the 7+3 combination cohort for newly diagnosed AML, 91% achieved complete remission, with 100% for NPM1-m patients and 83% for KMT2A-r patients. The study also noted high rates of minimal residual disease (MRD) negativity, with 76% in NPM1-m and 75% in KMT2A-r patients.

In the combination cohort with ven/aza for R/R AML, the overall response rate (ORR) for the NPM1-m population was 68%, with a composite complete remission (CRc) rate of 50%. Among NPM1-m patients with previous venetoclax exposure, the ORR was 50%, and the CRc was 36%. For KMT2A-r patients, 30% responded to the treatment, including those with prior venetoclax exposure.

Dr. Amer Zeidan of Yale Cancer Center, lead investigator of the KOMET-007 trial, emphasized the potential of ziftomenib in combination with standard treatments as an early intervention in AML, highlighting the high rates of complete remission and MRD negativity observed in the study. The rapid enrollment in the Phase 1a portion of the study underscores the urgency and enthusiasm for further evaluating this combination approach.

Kura and Kyowa Kirin have announced plans for a global, pivotal Phase 3 study, KOMET-017, evaluating ziftomenib in combination with standard treatments for adults with newly diagnosed KMT2A-r or NPM1-m AML. This study will include two independently powered, randomized, double-blind, placebo-controlled trials: one testing ziftomenib with ven/aza in a non-intensive therapy arm, and another testing ziftomenib with 7+3 in an intensive therapy arm. The KOMET-017 study is expected to begin in mid-2025.

The promising results from the KOMET-007 trial reinforce the commitment of Kura Oncology and Kyowa Kirin to advancing the clinical development of ziftomenib and improving treatment outcomes for AML patients. Dr. Mollie Leoni of Kura Oncology highlighted the importance of early therapy initiation to improve outcomes in AML, emphasizing the significant potential of ziftomenib in the frontline setting. Dr. Takeyoshi Yamashita of Kyowa Kirin underscored the substantial unmet medical need in AML, particularly for patients with NPM1 mutations, and the potential of ziftomenib to improve upon current treatment standards.

The encouraging data from the KOMET-007 trial mark a significant step forward in the development of new treatment options for AML patients, with the potential to transform care and improve patient outcomes.