A study of the drug "PRT2527" alone and in combination with zanubrutinib in various refractory and relapsed hematologic diseases

Aggressive B-cell lymphoma, mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Richter transformation, and T-cell lymphoma (TCL) are malignant diseases of the lymphatic and circulatory systems. In these conditions, lymphocytes—a type of white blood cell that is part of the body’s immune system—exhibit uncontrolled cell growth. The most common symptoms include swollen lymph nodes, an enlarged spleen, fatigue, exhaustion, fever, night sweats, and weight loss. The exact causes of these diseases are not fully understood, but genetic mutations, infections, and immune deficiencies may play a role. Treatment depends, among other factors, on the type and stage of the disease, as well as the patient’s age, physical condition, and symptoms; despite the various subtypes, treatment is often similar or the same. Standard treatment may include chemotherapy, immunotherapy, radiation therapy, or a stem cell transplant. Multiple forms of therapy may also be combined. In most cases, the goal is complete recovery from the disease. However, relapses after initial treatment are not uncommon. The disease may return (recurrence), or the conditions may become resistant to treatment (refractory). In such cases, intensifying the therapy is often recommended.

The goal of this Phase 1 study is to determine the most effective and safest dose of PRT2527 as monotherapy or in combination with zanubrutinib within a small, selected group of patients. PRT2527 inhibits the so-called CDK-19 protein in tumor cells, which is intended to stop their proliferation. The drug has not yet been approved for the treatment of these conditions. Zanubrutinib binds to and inhibits the so-called BTK protein in tumor cells, thereby also inhibiting their growth. Zanubrutinib is already approved, among other indications, for the treatment of MZL and CLL. During the escalation phase, PRT2527 is administered once a week as monotherapy in 21-day cycles or in combination with zanubrutinib once a week in cycles (first cycle: 35 days, followed by 28 days) as an infusion via a venous access site. After each cycle, the dose is increased until dose-limiting side effects occur. Once the most effective and safest dose has been determined, it will be further evaluated during a confirmation phase. The study is open-label, meaning that both the medical staff and the patient know which medications are being administered. Treatments and follow-up visits as part of the study will continue for up to 2 years, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated.

Patients aged 18 and older with aggressive B-cell lymphoma, mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Richter transformation, or T-cell lymphoma (TCL) are eligible to participate in this study. The disease must be refractory or recurrent, or patients must be unsuitable for standard treatment.