Pirtobrutinib

JAYPIRCA ® is a kinase inhibitor indicated for the treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor. Adult patients with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) with no known 17p deletion.

Pirtobrutinib is a small molecule, noncovalent inhibitor of BTK. BTK is a signaling protein of the B-cell antigen receptor (BCR) and cytokine receptor pathways. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. Pirtobrutinib binds to wild type BTK and BTK harboring C481 mutations, leading to inhibition of BTK kinase activity. In nonclinical studies, pirtobrutinib inhibited BTK-mediated B-cell CD69 expression and inhibited malignant B-cell proliferation. Pirtobrutinib showed dose-dependent anti-tumor activities in BTK wild type and BTK C481S mutant mouse xenograft models.

Recommended dosage: 200 mg orally once daily, swallow whole with water, with or without food. Do not cut, crush, or chew tablets. Manage toxicity using treatment interruption, dosage reduction, or discontinuation. Reduce dose in patients with severe renal impairment.

None. None.

Infections: Monitor for signs and symptoms of infection, evaluate promptly, and treat. Hemorrhage: Monitor for bleeding and manage appropriately. Cytopenias: Monitor complete blood counts during treatment. Cardiac Arrhythmias: Monitor for symptoms of arrhythmias and manage appropriately. Second Primary Malignancies: Other malignancies have developed, including skin cancers and other carcinomas. Monitor and advise patients to use sun protection. Hepatotoxicity, Including Drug-Induced Liver Injury: Monitor hepatic function throughout treatment. Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus and to use effective contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Infections Hemorrhage Cytopenias Atrial Fibrillation and Atrial Flutter Second Primary Malignancies Hepatotoxicity, including DILI Most common adverse reactions (≥ 30%), including laboratory abnormalities, are neutrophil count decreased and hemoglobin decreased.

Strong CYP3A Inhibitors: Avoid concomitant use. If concomitant use is unavoidable, reduce the JAYPIRCA dose. Strong or Moderate CYP3A Inducers: Avoid concomitant use. If concomitant use of moderate CYP3A inducers is unavoidable, increase the JAYPIRCA dose. Sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP Substrates: For substrates where minimal concentration changes may increase the risk of adverse reactions, follow recommendations for co-administration with CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP inhibitors provided in their approved product labeling.

Store JAYPIRCA tablets at room temperature 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) ().