AZD3470, a novel drug for the treatment of Hodgkin lymphoma (recurrence or persistent disease activity)

Classical Hodgkin lymphoma (cHL) is a malignant disease of the lymphatic system in which lymphocytes—a type of white blood cell that is part of the immune system—become cancerous. The most common symptoms include swollen lymph nodes, fever, night sweats, weight loss, and itching. This type of cancer often affects adolescents and young adults and is usually highly treatable. The exact causes of the disease are unclear, but genetic factors and infections such as the Epstein-Barr virus may play a role. Treatment depends on the stage of the disease and certain risk factors. Radiation therapy, chemotherapy, and immunotherapy are used. If the disease becomes active again after treatment (recurrence) or cannot be brought under control (refractory), further treatment is necessary. New, effective drugs are therefore being sought for this situation.  AZD3470 is a novel drug currently being investigated in clinical trials for the treatment of certain types of cancer. AZD3470 is a selective inhibitor of the enzyme PRMT5 (protein arginine methyltransferase 5). PRMT5 plays a role in gene regulation and is overactive in various types of cancer. By inhibiting PRMT5, AZD3470 aims to slow or stop the growth of cancer cells. The drug has not yet been approved for the treatment of cHL.

The goal of the PRIMAVERA study is to investigate the optimal dosage and efficacy of AZD3470 in cHL. In principle, patients with other conditions are also to be included in the study over time; however, the study is currently limited exclusively to patients with cHL. The study is a Phase 1/2 trial. In the first phase, the maximum tolerated dose (MTD) of AZD3470 will be determined. Subsequently, the dose of AZD3470 will be gradually increased, and the occurrence of side effects will be monitored (dose escalation). The medication is taken in tablet form in a 21-day cycle. All patients receive the same medication, and the study is open-label, meaning that both medical staff and patients know which medications are being administered. Treatment initially lasts for approximately one month (Phase 1 dose escalation). The primary endpoint of the first study phase is the occurrence of side effects that result in dose limitation. The study will last approximately two years in total.

Men and women aged 18 and older with cHL are eligible to participate in the first phase of the study (dose escalation). In the second phase (dose expansion), patients as young as 15 with cHL are also eligible to participate. The disease must show signs of recurrence or be uncontrollable (refractory). In addition, patients must have already undergone at least three lines of therapy, and there must be no involvement of the central nervous system (CNS: brain and spinal cord). If gastrointestinal symptoms are present, they must not interfere with the absorption of the medication.