Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Relapsed/Refractory Follicular Lymphoma: Results from the Phase 1/2 BRUIN Study

Background: Follicular lymphoma (FL) is a chronic and incurable disease requiring multiple lines of therapy for patients (pts) with relapsed/refractory (R/R) disease. Covalent Bruton tyrosine kinase inhibitors (cBTKi) have transformed the management of select B-cell malignancies, in particular chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). However, despite the transformative impact in CLL and MCL, the efficacy of single-agent cBTKi has been limited in pts with R/R FL, with an overall response rate (ORR) of 20.9% to 37.5% (Gopal et al, J Clin Oncol, 2018; Bartlett et al, Blood, 2018). Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi, inhibits both wildtype and C481-mutant BTK with equal low nM potency and has a favorable oral pharmacology that enables continuous BTK inhibition throughout the once-daily dosing interval. Pirtobrutinib has demonstrated promising efficacy and tolerability in pts with poor-prognosis B-cell malignancies following prior therapy, including cBTKi. Here, we report the safety and efficacy of pirtobrutinib in a cohort of pts with R/R FL from the BRUIN study (NCT03740529).