Dr Shah on the Background of the BRUIN Trial in Relapsed/Refractory MCL

Nirav N. Shah, MD, associate professor of medicine, the Division of Hematology and Oncology, the Medical College of Wisconsin, discusses the background of the phase 1/2 BRUIN trial (NCT03740529) of pirtobrutinib (Jaypirca) in patients with heavily pretreated, relapsed/refractory mantle cell lymphoma (MCL).

At the 2023 ASCO Annual Meeting, Shah and colleagues presented updated data and a subgroup analysis from the phase 1/2 trial. In the cohort of 90 patients with MCL who received prior treatment with a BTK inhibitor, pirtobrutinib elicited an overall response rate (ORR) of 56.7% (95% CI, 45.8%-67.1%), with complete response (CR) and partial response (PR) rates of 18.9% and 37.8%, respectively. In a cohort of 14 patients with BTK inhibitor–naïve MCL, the ORR was 85.7% (95% CI, 57.2%-98.2%). The CR and PR rates were both 42.9%.

In January 2023, the FDA approved pirtobrutinib for use in adult patients with relapsed or refractory MCL following at least 2 lines of systemic therapy, including a BTK inhibitor. This approval was supported by prior findings from the MCL subset of patients enrolled to the BRUIN trial.

BRUIN was a large, open-label, single-arm phase 1/2 clinical trial, which evaluated pirtobrutinib, a noncovalent BTK inhibitor, Shah begins. Compared with previous covalent BTK inhibitors previously approved for the treatment of patients with MCL, noncovalent agents have a different mechanism, he adds. This trial was unique in that it allowed patients who had prior exposure to a covalent BTK inhibitor to enroll onto the clinical trial, he concludes.