On December 1, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pirtobrutinib (Jaypirca) for adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor and a BCL2 inhibitor.
BRUIN Trial
Efficacy was evaluated in BRUIN (ClinicalTrials.gov identifier NCT03740529), an open-label, international, single-arm, multicohort trial that included 108 patients with CLL or SLL previously treated with at least two prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor. Patients had received a median of five prior lines of therapy (range = 2–11). Seventy-seven percent of patients discontinued the last BTK inhibitor for refractory or progressive disease. Pirtobrutinib was administered orally at 200 mg once daily and was continued until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate and duration of response, as assessed by an independent review committee using 2018 International Workshop on Chronic Lymphocytic Leukemia criteria. The overall response rate was 72% (95% confidence interval [CI] = 63%–80%) and the median duration of response was 12.2 months (95% CI = 9.3–14.7 months). All responses were partial responses.
The most common adverse reactions in patients receiving pirtobrutinib (≥ 20%), excluding laboratory terms, were fatigue, bruising, cough, musculoskeletal pain, COVID-19 infection, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities in > 10% of patients were decreased neutrophil counts, anemia, and decreased platelet counts. Serious infections occurred in 32% of patients, including fatal infections in 10%.
Pirtobrutinib’s prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.
The recommended pirtobrutinib dose is 200 mg orally once daily until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review and Orphan Drug designation.
