Final Analysis of the
BRUIN
Phase 1/2 Study Assessing the Safety and Efficacy of Pirtobrutinib Monotherapy in Patients With
MCL
Michael L. Wang, Jonathon B. Cohen, Nirav N. Shah, Wojciech Jurczak, Pier Luigi Zinzani, Chan Y. Cheah, Chaitra S. Ujjani, Youngil Koh, Won Seog Kim, Sunita D. Nasta, Ian Flinn, Benoit Tessoulin, Shuo Ma, Alvaro J. Alencar, David J. Lewis, Jennifer A. Woyach, Kami J. Maddocks, Krish Patel, Yucai Wang, Joanna M. Rhodes, Constantine S. Tam, John F. Seymour, Hirokazu Nagai, Julie M. Vose, Bita Fakhri, Marc S. Hoffmann, Francisco Hernandez‐Ilizaliturri, Andrew D. Zelenetz, Anita Kumar, Talha Munir, Donald E. Tsai, Paolo Abada, Minna Balbas, Jian Li, Denise Wang, Lindsey E. Roeker, Toby A. Eyre ABSTRACT
Pirtobrutinib, a highly selective, non‐covalent Bruton tyrosine kinase inhibitor (BTKi) previously demonstrated durable efficacy and tolerable safety following covalent (c) BTKi therapy in heavily pretreated relapsed/refractory (R/R) mantle cell lymphoma (MCL). Here, we report final results from the global Phase 1/2 BRUIN trial evaluating pirtobrutinib in patients with R/R MCL, with and without prior cBTKi exposure. Endpoints included overall response rate (ORR), duration of response (DOR), progression‐free survival (PFS), overall survival (OS), and safety. BRUIN enrolled 166 patients with R/R MCL (data cutoff: 27Jan2025). In the cBTKi‐exposed cohort ( n = 152), median study follow‐up time was 16.1 months (range, 0.5–69.6). The ORR was 49.3% (95% CI, 41.1–57.6). Median DOR was 21.6 months (95% CI, 9.2–27.2). Median PFS was 5.6 months (95% CI, 5.3–9.2; 36‐month rate, 19.9%). Median OS was 23.9 months (95% CI, 17.3–51.5; 36‐month rate, 43.2%). In the cBTKi‐naïve cohort ( n = 14), median study follow‐up time was 44.5 months (range, 1.6–67.1). The ORR was 85.7% (95% CI, 57.2–98.2). Median DOR was 42.7 months (95% CI, 25.8–not estimable [NE]). Median PFS was 44.6 months (95% CI, 16.7–NE; 36‐month rate, 58.7%). Median OS was NE (36‐month rate, 76.2%). The most frequent any‐grade treatment‐emergent adverse events (TEAEs) were infections (44.0%), fatigue (31.9%), and diarrhea (22.9%); the most frequent grade ≥ 3 TEAEs were infections (21.1%) and neutropenia (15.1%). Grade ≥ 3 hemorrhage (3.0%) and any‐grade atrial fibrillation/flutter (3.6%) were infrequent. With extended follow‐up, pirtobrutinib continued to demonstrate efficacy and favorable safety in cBTKi‐exposed and ‐naïve R/R MCL.
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