New drug ziftomenib for relapsed or refractory acute myeloid leukemia with specific genetic alterations

Acute myeloid leukemia (AML) is a rapidly progressing form of cancer. In this disease, immature white blood cells (blasts) multiply uncontrollably in the bone marrow and suppress normal blood cell production. People with AML often experience fatigue, a heightened susceptibility to infections, and a tendency to bleed. Standard treatment includes intensive chemotherapy, a stem cell transplant, or targeted therapies. Despite these treatments, some patients experience a relapse. In other cases, the disease does not respond adequately to therapy (refractory). Therefore, new treatment approaches are urgently needed. Various genetic alterations in the leukemia cells may play a role in the development of AML. These include, among others, alterations in the KMT2A gene (so-called KMT2A gene rearrangements) and mutations in the NPM1 gene. Both genetic alterations are associated with the protein menin. Menin regulates signaling pathways that promote the growth and proliferation of leukemia cells. Ziftomenib is a novel menin inhibitor. It specifically blocks this protein and is thus intended to disrupt the pathological signaling pathways. The drug is taken as a tablet and is not yet approved for treatment in the EU.

The goal of this Phase 1/2 study is to investigate the safety and efficacy of the novel drug ziftomenib in patients with relapsed or refractory AML. To this end, the study is divided into a main study and four substudies. In the main study, ziftomenib will be evaluated in patients with relapsed or refractory AML. In Phase 1a, the maximum tolerated dose—or the dose recommended for Phase 2—will be determined; this dose will then be further evaluated for safety, tolerability, and biological activity in the subsequent Phase 1b. In Phase 2, the efficacy of ziftomenib will be evaluated in patients with NPM1-mutated AML. Additional substudies will examine, among other things, interactions with other medications often used in conjunction with AML therapy, such as midazolam (substudy 1) and itraconazole (substudy 2), as well as its use in acute lymphoblastic leukemia (ALL) with KMT2A gene rearrangement (substudy 3) and in patients with AML and specific genetic alterations (substudy 4). The study is open-label, which means that both the patients and the treating study physicians know which treatment is being administered. A total of approximately 263 people are expected to participate in the study. Recruitment for the main study has already been completed.

Women and men aged 18 and older with relapsed or refractory acute myeloid leukemia and specific genetic alterations are eligible to participate in this study. For Substudy 3, patients with relapsed or refractory acute lymphoblastic leukemia and specific genetic alterations may participate.