CLL Coverage from Every Angle

SOHO 2021: Early-Phase Results With Novel BTK Inhibitor in CLL

By: Lauren Harrison, MS
Posted: Wednesday, September 22, 2021

Pirtobrutinib (LOXO-305), a selective, noncovalent, Bruton’s tyrosine kinase (BTK) inhibitor, showed activity in patients with pretreated chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL). Catherine C. Coombs, MD, of the University of North Carolina at Chapel Hill, presented results from this ongoing phase I/II BRUIN trial during the 2021 Society of Hematologic Oncology (SOHO) Annual Meeting (Abstract CLL-039).

The trial enrolled 170 patients with CLL or SLL, plus 153 patients with other B-cell malignancies. Patients were administered oral pirtobrutinib at a dose of 25 to 300 mg across seven dose-escalation levels once a day in 28-day cycles. Pirtobrutinib achieved high oral exposures, and doses higher than 100 mg daily exceeded BTK IC90 (concentration of the drug required for 90% inhibition) for the entire dosing interval. Therefore, a dose of 200 mg daily was selected as the recommended phase II dose.

The objective response rate among the entire study population was 63%, as 69 patients had a partial response, 19 had a partial response with rebound lymphocytosis, 45 had stable disease, 1 had progressive disease, and 5 discontinued therapy before assessment of the first response. These responses appeared to deepen over time, and the objective response rate was 86% among patients who had at least 10 months of follow-up. One patient has remained on therapy for at least 17.8 months and continues to have a response.

The most common treatment-emergent adverse events of any grade were fatigue (20%), diarrhea (17%), and contusion (13%). There were no dose-limiting toxicities observed.

Disclosure: No disclosure information was provided.

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