FDA Approves First Noncovalent BTK Inhibitor Pirtobrutinib for MCL

By Kerri Fitzgerald - Last Updated: January 27, 2023

The U.S. Food and Drug Administration (FDA) approved pirtobrutinib, the first and only noncovalent Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of relapsed/refractory mantle cell lymphoma (MCL) after two lines of systemic therapy, including a BTK inhibitor.

The decision was based on findings from the ongoing, open-label, single-arm, international, multicenter, phase I/II BRUIN trial. The efficacy analysis included 120 patients with MCL who were treated with pirtobrutinib 200 mg once daily until disease progression or unacceptable toxicity. Patients received a median of three prior lines of therapy (range, 1-9 therapies), and all received one or more prior lines of therapy containing a covalent BTK inhibitor. Most patients (83%) had discontinued their last BTK inhibitor due to refractory or progressive disease.

Among the patient cohort studied, the overall response rate was 50% (n=60), including 15 complete responses (13%) and 45 partial responses (38%). Median time to response was 1.8 months (range, 0.8-4.2 months), and the median duration of response was 8.3 months (range, 5.7 to not estimable).

The safety analysis included 128 patients with MCL, 36% of whom were treated for six or more months, and 10% of whom were treated for at least a year. Adverse events led to dose reductions in 4.7% of patients and permanent treatment discontinuations in 9% of patients. Serious adverse events occurred in 38% of patients, and serious adverse reactions that occurred in 2% or more patients included pneumonia (14%), COVID-19 (4.7%), musculoskeletal pain (3.9%), hemorrhage (2.3%), pleural effusion (2.3%), and sepsis (2.3%).

Pirtobrutinib was approved under the FDA’s Accelerated Approval pathway. A confirmatory phase III trial (BRUIN MCL-321) is currently enrolling patients.

Source: Eli Lilly press release, January 2023

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