On January 27, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pirtobrutinib (Jaypirca) for patients with relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor.
Efficacy was evaluated in BRUIN (ClinicalTrials.gov identifier NCT03740529), an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that included 120 patients with mantle cell lymphoma previously treated with a BTK inhibitor. Patients had a median of three prior lines of therapy, with 93% having received two or more prior lines. The most common prior BTK inhibitors received were ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%); 83% of patients had discontinued their last BTK inhibitor due to 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 measures were overall response rate and duration of response, as assessed by an independent review committee using Lugano criteria.
The overall response rate was 50% (95% confidence interval [CI] = 41%–59%), with a complete response rate of 13%. The estimated median duration of response was 8.3 months (95% CI = 5.7 months to not evaluable), and the estimated duration of response rate at 6 months was 65.3% (95% CI = 49.8%–77.1%).
The most common adverse reactions (≥ 15%) in patients with mantle cell lymphoma were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities occurring in ≥ 10% of patients were decreased neutrophil counts, lymphocyte counts, and platelet counts. The prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies.
The recommended pirtobrutinib dosage 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, Fast Track designation, and Orphan Drug designation.