To evaluate the safety and efficacy of pirtobrutinib in previously treated patients (pts) with MCL.

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.

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 (25-300mg 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.

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. Previously presented at American Society of Hematology - 63rd Annual Meeting.