A Study Comparing the New Drug Pirtobrutinib with Standard Treatment for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are very similar types of cancer that originate in the B cells of the immune system. B cells are a subtype of white blood cells and are responsible for fighting pathogens, for example. In CLL/SLL, abnormal B cells accumulate in the blood, bone marrow, and lymph nodes, which can lead to symptoms such as fatigue, a tendency to develop infections, and enlarged lymph nodes. Under a microscope, the tumor cells of CLL and SLL are indistinguishable; however, in chronic lymphocytic leukemia, unlike in SLL, the cells are also found in the blood. Treatment of these diseases depends on the symptoms and may involve simply monitoring laboratory values, chemotherapy, immunotherapy, or, in rare cases, stem cell therapy. Ibrutinib is a commonly used medication that inhibits the activity of the BTK (Bruton’s tyrosine kinase) protein, thereby preventing the growth of cancer cells. In some cases, resistance develops over time, and the medication loses its effectiveness. Pirtobrutinib is a new drug that also targets Bruton’s tyrosine kinase but binds to and inhibits the protein at a different site. It is therefore expected to be effective even in cases of resistant or relapsed CLL/SLL.

The goal of this Phase 3 study is to investigate the efficacy and safety of pirtobrutinib in a direct comparison with ibrutinib. Patients will be randomly assigned to two treatment groups. One group will receive pirtobrutinib and the other ibrutinib. Treatment with pirtobrutinib is divided into two phases. Only patients with a specific genetic alteration (17p deletion) may participate in the second phase. The study is open-label, meaning that both medical staff and patients know which treatment is being administered. After the study begins, patients will be regularly monitored by the medical staff. The study will compare disease-free survival, overall survival, and the magnitude of the therapeutic effect between the two groups. Phase 1 lasts up to 6 years, and Phase 2 lasts up to 2 years.

Women and men aged 18 and older with a confirmed diagnosis of chronic lymphocytic leukemia or small-cell lymphocytic lymphoma requiring treatment are eligible to participate in the study. The disease may have been previously treated or newly diagnosed. Prior to participation, a preliminary test for the 17p deletion genetic alteration must have been performed.