New Targeted Therapy for Advanced Blood Cancers with Specific Genetic Alterations: Study on the Drug AZD3632

Acute leukemia and myelodysplastic syndrome (MDS) are malignant disorders of the hematopoietic system. Blood cancers originate in the bone marrow, where new blood cells are normally produced. In diseases such as AML or MDS, immature or abnormal blood cells multiply uncontrollably and displace the healthy cells. In many blood cancers, certain genes (HOX genes, KMT2Ar, or NPM1m) play a key role because they drive the uncontrolled growth of cancer cells. The study drug AZD3632 is designed to specifically target cancer cells that exhibit these specific genetic alterations. In this study, the active ingredient AZD3632 is being tested in humans for the first time (first-in-human).

The goal of this Phase 1/2 study is to investigate the safety, tolerability, and efficacy of the new drug AZD3632. The study consists of two parts (modules). In Module 1, AZD3632 is tested as a single therapy (monotherapy). Different doses will be tested sequentially to determine the maximum tolerated dose (dose escalation). There are six dose groups. In Module 2, the study will examine how AZD3632 behaves when taken together with posaconazole. Posaconazole is a medication used to treat and prevent fungal infections; it is frequently used in people with weakened immune systems, including patients with leukemia. Since posaconazole can affect the breakdown of other drugs in the body, it is important to know whether and how it alters the concentration of AZD3632 in the blood. AZD3632 is taken as a tablet. Patients will be closely monitored to detect side effects early on. At the same time, the study will examine how the body absorbs and metabolizes the medication (pharmacokinetics) and whether it has the desired effect on cancer cells (preliminary efficacy).

Adults and adolescents aged 16 and older with acute leukemia or myelodysplastic syndromes (MDS) who are no longer responding to standard therapies (refractory) or whose disease has returned (relapsed) are eligible to participate. A prerequisite is evidence of one of the specified genetic alterations (KMT2A rearrangement, NPM1 mutation, or other alterations leading to HOX overexpression).