Successful Results for Pirtobrutinib in Previously Treated CLL Patients

Updated data from the Phase I/2 BRUIN study has shown a favorable response of pirtobrutinib (LOXO-305) in pretreated CLL patients. Pirtobrutinib is a highly potent BTK inhibitor that blocks the activity that leads to growth of the B-cells which leads to cell death of the cancerous B-cells. The BRUIN trial includes one of the largest prospective cohorts of BTK inhibitor pre-treated CLL/SLL patients ever studied. The trial is looking at the use of the oral medication, pirtobrutinib, for patients with advanced B-cell cancers like CLL that have received two or more lines of therapy. A total of 252 patients were enrolled in this study who had active CLL that had been pretreated without success. Pirtobrutinib was dose escalated in 28 day cycles.

Information About the Patients Enrolled:

• Patients an average of 3 lines of previous treatment
• All patients had received a BTK inhibitor
• 88% had received a CD20 antibody
• 79% had received chemotherapy
• 41% had received a BCL-2 inhibitor
• 20% had received a a PI3K inhibitor
• 6% had a prior CAR-T therapy
• 6 patients underwent a stem cell transplant

What Has Been Found So Far?

“Pirtobrutinib was well tolerated and demonstrated promising effectiveness in patients with CLL and SLL regardless of prior therapy, number of prior lines of therapy or BTK C481 mutation status.” Data showed that the overall response rate (ORR) for BTK pretreated patients was 68%. For those who responded to the treatment:

• 1% achieved complete response (CR)
• 54% achieved partial response (PR)
• 13% had partial response with rebound lymphocytosis
• 25% had stable disease

“Responses were also consistent regardless of the prior therapy. You can see that it was consistent for the double-exposed population, but even in the so-called pentavalent-refractory patient population” stated Dr. Anthony Mato from Memorial Sloan Kettering Center. Even those patients who had been previously treated with: a BTK inhibitor, venetoclax, chemoimmunotherapy, or a PIK3 inhibitor, showed consistent responses.

Responses to treatment deepened over time with an overall response rate of 73% at the 12-month mark. Safety statistics showed that 96% of patients received at least one dose of pirtobrutinib of 200 mg daily. Fatigue, diarrhea, and neutropenia were the most frequent side effects. For a majority of patients, pirtobrutinib showed a favorable safety and tolerability profile.

Recruitment Status for this Study is Still Open. It Includes 3 Parts:

• Phase I- pirtobrutinib monotherapy dose escalation
• Phase Ib- pirtobrutinib in combination therapy
• Phase 2- patients will be enrolled in one of seven dose expansion groups

860 participants are projected with a study completion timeline in October 2023. To learn more about this ongoing study and to find the facilities where the trial is available, click here.