Pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor in previously treated mantle cell lymphoma: updated results from the phase 1/2 BRUIN study.

Aim: To evaluate the safety and efficacy of pirtobrutinib in previously treated patients (pts) with MCL. Method: BRUIN is a multicenter phase 1/2 study (NCT03740529) of oral pirtobrutinib monotherapy in pts with advanced B-cell malignancies who have received >2 prior therapies. The primary objective for phase 1 was to determine the RP2D. The primary objective of phase 2 was ORR. Secondary objectives included DoR, PFS, OS, safety and tolerability, and pharmacokinetics. Results: As of 27 Sept 2020, 323 pts (170 CLL/SLL, 61 MCL, 26 WM, 26 DLBCL, 13 MZL, 12 FL, 9 RT and 6 other NHL) were treated on 7 dose levels (25-300 mg QD). Among the 61 MCL pt, median number of prior lines of therapy was 3 (1-8). No DLTs were reported and MTD was not reached (n = 323). 200mg QD was selected as the RP2D. Fatigue (20%), diarrhea (17%) and contusion (13%) were the most frequent TEAEs regardless of attribution or grade seen in >10% pts. The most common AE of grade ≥3 was neutropenia (10%). Treatment-related hemorrhage/hypertension occurred in 5 (2%)/4 (1%) pts. 5 (1%) pts discontinued due to TEAEs. 52 prior BTKi treated MCL pts were efficacy evaluable with an ORR of 52% (95% CI 38-66; 13 CR (25%), 14 PR (27%), 9 SD (17%), 11 PD (21%) and 5 (10%) discontinued prior to first response assessment). Median follow up was 6 months (0.7-18.3+). Responses were observed in 9/14 pts (64%) with prior autologous or allogeneic stem cell transplant, and 2 of 2 with prior CAR-T cell therapy. Conclusion: Pirtobrutinib demonstrated promising efficacy in heavily pretreated, poor-prognosis MCL following multiple prior lines of therapy. Pirtobrutinib was well tolerated and exhibited a wide therapeutic index. Updated data, including approximately 60 new pts with MCL and an additional 10 months since the prior data cut will be presented. [ABSTRACT FROM AUTHOR]