Multicenter phase 2 trial of pirtobrutinib for relapsed or refractory B-cell malignancies in Chinese patients

Pirtobrutinib is a selective reversible (noncovalent) Bruton tyrosine kinase inhibitor (BTKi). A phase 2 trial at 19 centers in China evaluated pirtobrutinib for covalent BTKi (cBTKi) pretreated relapsed or refractory (R/R) B-cell malignancies in three cohorts. All patients received pirtobrutinib monotherapy 200 mg once daily till progression or unacceptable toxicity. Primary endpoint was overall response rate. In the mantle cell lymphoma cohort (n=35), overall response rate was 62.9% (95% CI 44.9-78.5), with median duration of response, progression-free survival, and overall survival not reached, 6.8 months, and 15.5 months, respectively. In the CLL/SLL cohort (n=11), the ORR was 63.5% (95% CI 30.8-89.1) with 12-months duration of response rate 83.5% (95% CI 27.3-97.5). In the safety population (n=87), the most common adverse events were anemia (32.3%) and decrease of neutrophil count (31.0%). The authors conclude that pirtobrutinib demonstrated clinically meaningful efficacy in Chinese patients with cBTKi pretreated R/R MCL, preliminary antitumor activity in cBTKi pretreated R/R CLL/SLL, and was generally well-tolerated.