Komzifti (ziftomenib)

Among them, revumenib and ziftomenib have advanced furthest in clinical testing. Ongoing trials are now evaluating menin inhibitors in rational combinations, frontline regimens, and maintenance therapy. Collectively, these advances highlight menin inhibition as a transformative strategy in acute leukemia, reshaping therapy through precision-targeted epigenetic intervention.

P3, N=1300, Recruiting, Kura Oncology, Inc. | Not yet recruiting --> Recruiting

Ziftomenib demonstrated significant clinical benefit and deep responses in patients with heavily pretreated, relapsed/refractory NPM1-m AML. Ziftomenib was well tolerated with a safety profile consistent with previous studies, including manageable differentiation syndrome, lack of clinically significant QTc prolongation, and low rates of myelosuppression.

P1, N=420, Recruiting, Kura Oncology, Inc. | N=212 --> 420 | Trial completion date: May 2027 --> Apr 2030 | Trial primary completion date: May 2026 --> Apr 2030

These findings justify the integration of menin inhibitors into the AML therapeutic landscape, and support ongoing randomized trials to confirm their benefit in both frontline and relapse or refractory settings.

P1, N=44, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

Currently, six menin inhibitors are in clinical evaluation as monotherapy or in combination regimens: revumenib, ziftomenib, bleximenib (previously JNJ-75276617), enzomenib (previously DSP-5336), DS-1594, and BMF-219. We discuss their efficacy, safety profiles, and potential roles within the current treatment algorithm. The continued clinical evaluation of menin inhibitors may redefine treatment paradigms for NPM1m and KMT2Ar AML and other acute leukemia with the aberrant MEIS1-HOXA axis, offering new hope for patients with limited therapeutic options.

Novel investigational agents in current clinical trials are also highlighted, along with the roles of exportin 1 (XPO1), menin-KMT2A inhibitors and immunotherapy in NPM1-mutated AMLs. This review focuses on critically evaluating the available data and aims to reveal the secrets of NPM1-mutated AMLs.

P1/2, N=263, Recruiting, Kura Oncology, Inc. | N=199 --> 263

Following the promising outcomes of the two pioneering menin inhibitors, revumenib and ziftomenib, other menin inhibitors, including bleximenib, enzomenib, BN-104 and HMPL-506 are currently under investigation in clinical trials. Several trials presented their initial outcomes at the 2024 ASH Annual Meeting. This review highlights the key outcomes of these pivotal clinical trials.

P3, N=1300, Not yet recruiting, Kura Oncology, Inc.

Menin inhibitors demonstrate promising clinical activity in molecularly defined leukemias, with Revumenib establishing proof-of-concept for this therapeutic approach. However, challenges remain, including resistance development, optimal timing of therapy initiation, and determination of effective combination strategies. Larger randomized trials with extended follow-up are needed to establish long-term efficacy and safety profiles. The rapid clinical development of multiple agents in this class suggests an expanding role for Menin inhibitors in leukemia treatment paradigms.