To evaluate the safety and efficacy of pirtobrutinib in previously treated CLL/SLL.

BRUIN is a phase 1/2 multicenter study (NCT03740529) of oral pirtobrutinib monotherapy in pts with advanced B-cell malignancies who have received ≥ 2 prior therapies. Primary objective for phase 1: determine the RP2D. Primary objective of phase 2: ORR. Secondary objectives included DoR, PFS, OS, safety and tolerability and pharmacokinetics.

As of 27 Sept 2020, 323 pts with B-cell malignancies (170 CLL/SLL, 61 MCL, 26 WM, 26 DLBCL, 13 MZL, 12 FL, 9 RT and 6 other) were treated on 7 dose levels (25-300mg QD). Median number of prior lines of therapies=3 (1-11). No DLTs were reported and MTD was not reached (n = 323). 200mg QD was selected as RP2D. Fatigue (20%), diarrhea (17%) and contusion (13%) were the most frequent TEAEs regardless of attribution or grade seen in ≥ 10% pts. Most common AE of grade ≥3 was neutropenia (10%). 139 CLL/SLL pts were efficacy-evaluable with a median follow up time of 6 months (0.16-17.8+). ORR was 63% (95%CI 55-71) with 69 PRs (50%), 19 PR-Ls (14%), 45 SDs (32%) and 1 PD (1%), and 5 (4%) discontinued prior to first response assessment. Among 121 BTKi pretreated pts, ORR was 62% (95%CI 53-71). Responses deepened over time with an ORR of 86% among pts with ≥ 10 months follow-up. ORR was similar in pts who discontinued prior BTKi due to progression (67%), or adverse events or other reasons (52%). Of 88 responding pts, all except 5 remained on therapy.

Pirtobrutinib demonstrated promising efficacy in heavily pretreated CLL/SLL pts. Pirtobrutinib was well tolerated and exhibited a wide therapeutic index. Updated data, including approximately 100 new pts with CLL and an additional 10 months since the prior data cut will be presented. Previously presented at the American Society of Hematology - 63rd Annual Meeting.