Pirtobrutinib for Previously Treated Blood Cancer (CLL/SLL): Efficacy and Safety of Three Dosages

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are closely related cancers of the lymphatic system. Both are slow-growing diseases in which certain white blood cells (B cells) grow uncontrollably. These cancer cells can weaken the immune system, lead to infections, and displace other healthy cells in the blood. An important treatment approach for CLL/SLL is the inhibition of the enzyme Bruton’s tyrosine kinase (BTK), which is essential for the survival of cancer cells. Drugs that block BTK (e.g., ibrutinib) have proven effective, but many patients develop resistance or intolerance over time.

Pirtobrutinib is a newly developed, so-called non-covalent BTK inhibitor. It works differently from covalent BTK inhibitors and can remain effective even when covalent inhibitors are no longer effective. The primary objective of this study is to evaluate the efficacy and safety of three different doses of pirtobrutinib in participants with recurrent (relapsed) CLL or SLL or CLL or SLL that has not responded to previous treatments. To be eligible for participation, participants must have already undergone one to three prior treatments, including therapy with a so-called covalent BTK inhibitor.

The study is open-label, meaning that both the medical team and the participants know which dose is being administered. The study drug, pirtobrutinib, is taken daily and treatment may continue for up to three years, as long as the patient benefits from it and no serious side effects occur. The follow-up period also spans the entire study duration of up to three years, during which regular checkups will take place.

Eligible participants include women and men aged 18 and older with confirmed CLL or SLL who have already received 1 to 3 prior therapies—including treatment with a covalent BTK inhibitor—and who currently require further treatment. They must be in good general health and able to take tablets. Excluded are individuals who have already been treated with a non-covalent BTK inhibitor or a BTK degrader, who have experienced severe bleeding while on BTK therapy, or who are suspected of having a more aggressive form of the disease (Richter transformation) or central nervous system involvement.