Pirtobrutinib has shown clinical activity in relapsed or refractory mantle cell lymphoma (MCL), according to study results published in the Journal of Clinical Oncology.
Pirtobrutinib produced durable responses in patients who had previously received treatment with a covalent BTK inhibitor (cBTKi) and in patients who were cBTKi-naïve, researchers reported.
This phase 1/2 trial (ClinicalTrials.gov Identifier: NCT03740529) included 164 MCL patients. In the phase 1 portion, patients received pirtobrutinib at doses ranging from 25 mg to 300 mg once daily.
In the phase 2 portion, patients received pirtobrutinib at the recommended dose of 200 mg daily. They were treated until disease progression or unacceptable toxicity, though patients with progression could continue on pirtobrutinib at the investigator’s discretion.
The efficacy population included 90 patients who had previously received treatment with a cBTKi and 14 patients who had not. Patients in the cBTKi-pretreated group had received a median of 3 prior lines of therapy (range, 1-8), and patients in the cBTKi-naïve group had received a median of 2 prior lines of therapy (range, 1-3).
In the cBTKi-pretreated patients, the overall response rate (ORR) was 57.8%. There were 18 complete responses and 34 partial responses. In the cBTKi-naïve patients, the ORR was 85.7%. There were 5 complete responses and 7 partial responses.
In the cBTKi-pretreated patients, the median duration of response was 21.6 months at a median follow-up of 11.9 months, and 35% of responses were ongoing at the data cutoff. In the cBTKi-naïve patients, the median duration of response was not reached at a median follow-up of 7.1 months.
In the cBTKi-pretreated patients, the median progression-free survival (PFS) was 7.4 months at a median follow-up of 9.2 months. The median overall survival (OS) was not reached at a median follow-up of 16.6 months.
In the cBTKi-naïve patients, the median PFS was not reached at a median follow-up of 8.6 months. The median OS was not reached at a median follow-up of 9.4 months.
All 164 patients were evaluable for safety. The most common treatment-emergent adverse events (TEAEs) were fatigue (29.9%), diarrhea (21.3%), and dyspnea (16.5%). The most common grade 3 or higher TEAE was neutropenia (13.4%).
Treatment discontinuations due to TEAEs occurred in 15 patients (9.1%). There were 11 fatal TEAEs, but none were considered related to treatment.
“In summary, pirtobrutinib is the first non-covalent (reversible) BTK inhibitor to demonstrate meaningful response rates and durable efficacy in patients with heavily pre-treated MCL who received a prior cBTKi,” the researchers concluded.
Disclosures: This research was supported by Loxo Oncology Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Wang ML, Jurczak W, Zinzani PL, et al. Pirtobrutinib in covalent BTK-inhibitor pre-treated mantle cell lymphoma. J Clin Oncol. Published online May 16, 2023. doi:10.1200/JCO.23.00562