FDA Grants Accelerated Approval to Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma
On January 27, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-relapsed-or-refractory-mantle-cell-lymphoma) to pirtobrutinib (Jaypirca®) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor.
Efficacy was evaluated in BRUIN (NCT03740529), an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that included 120 patients with MCL previously treated with a BTK inhibitor. Patients had a median of three prior lines of therapy, with 93% having two or more prior lines. The most common prior BTK inhibitors received were ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%). Eighty-three percent of patients had discontinued their last BTK inhibitor because of refractory or progressive disease. Pirtobrutinib was administered orally at 200 mg once daily until patients experienced disease progression or unacceptable toxicity.
The main efficacy measures were overall response rate (ORR) and duration of response (DOR), as assessed by an independent review committee using Lugano criteria. The ORR was 50% (95% CI = 41, 59) with a complete response rate of 13%. The estimated median DOR was 8.3 months (95% CI = 5.7, NE), and the estimated DOR rate at six months was 65.3% (95% CI = 49.8, 77.1).
The most common adverse reactions reported in at least 15% of patients in the clinical trial were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. Grade 3 or 4 laboratory abnormalities reported in at least 10% of patients in the trial were decreased neutrophil, lymphocyte, 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 patients experience disease progression or unacceptable toxicity.
The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate the FDA’s assessment.
The application was granted priority review and fast track designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics). The application also was granted orphan drug designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).