The following article features coverage from the 2021 Annual Meeting of the Society of Hematologic Oncology (SOHO). Click here to read more of Cancer Therapy Advisor’s conference coverage.

Pirtobrutinib is well tolerated and shows promising efficacy in patients with B-cell malignancies, particularly in heavily pretreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to study results presented at the Annual Meeting of the Society of Hematologic Oncology (SOHO).

Researchers presented safety and efficacy data of a cohort of patients from BRUIN, an ongoing, multicenter, phase 1/2 trial evaluating pirtobrutinib (LOXO-305), a highly selective noncovalent BTK inhibitor.

A total of 323 previously treated patients with B-cell malignancies (including 170 patients with CLL or SLL) have been enrolled thus far. Oral pirtobrutinib was administered in 7 dose escalation levels (25-300 mg once daily) in 28-day cycles.

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Pirtobrutinib showed high oral exposures, with doses ≥100 mg once per day exceeding BTK IC90 for the entire dosing interval. Fatigue (20%), diarrhea (17%), and contusion (13%) were the treatment-emergent adverse events (TEAEs) that occurred in ≥10% of the 323 patients, and 5 patients (1.5%) discontinued owing to TEAEs. No dose-limiting toxicities were reported, and the recommended phase 2 dose was 200 mg once per day.

The 170 patients with CLL or SLL had a median age of 69 (36-88) years, and 64% were male. About 90% had previously used anti-CD20 antibody therapy, 86% had previously used a BTK inhibitor, and 82% had previous chemotherapy.

Among the 139 efficacy-evaluable patients with CLL or SLL, the overall response rate (ORR) was 63%, 0% of patients had a complete response, and 50% had a partial response. The responses strengthened over time in patients with ≥10 months of follow-up (n=29; ORR, 86%). The median follow-up was 6 months (range, 0.6-17.8+) in this cohort.

The responses were observed across all dose levels, according to the investigators. Efficacy was independent of BTK C481 mutation status, the reason for prior BTK inhibitor discontinuation, or other classes of prior therapy received.

“The favorable safety and tolerability are consistent with the design of pirtobrutinib as a highly selective and noncovalent BTK inhibitor,” stated the study authors. “Notable covalent BTK inhibitor-associated toxicities were rarely observed.”

Disclosure: This study was sponsored by Loxo Oncology at Lilly.

Read more of Cancer Therapy Advisor’s coverage of SOHO 2021 by visiting the conference page.


Coombs CC, Pagel JM, Shah NN, et al. Pirtobrutinib (LOXO-305), a next generation, highly selective, non-covalent BTK inhibitor in previously treated CLL/SLL: results from the phase 1/2 BRUIN study. Paper presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 8-11, 2021. Abstract CLL-039.

This article originally appeared on Hematology Advisor