Pirtobrutinib Monotherapy Earns Canadian Approval in Lymphoma/Leukemia Populations

Pirtobrutinib (Jaypirca) has earned Canadian approval as a monotherapy for the treatment of adult patients with relapsed/refractory mantle cell lymphoma (MCL) previously treated with 2 or more prior lines of systemic therapy including a Bruton tyrosine kinase (BTK) inhibitor or those with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received 2 or more prior lines systemic therapy including a BTK inhibitor and a BCL-2 inhibitor, according to a news release from the developer, Eli Lilly Canada.¹

CLL/SLL Population

Supporting the Notice of Compliance with conditions (NOC/c) are efficacy data from the phase 1/2 BRUIN trial (NCT03740529) previously published in the New England Journal of Medicine.² Therein, among 247 evaluable patients with CLL/SLL, the overall response rate (ORR) was 73.3% (95% CI, 67.3%-78.7%), and included 4 complete responses (CRs), 1 nodular partial response (PR), and 176 PRs. When accounting for PR with lymphocytosis, the ORR was 82.2% (95% CI, 76.8%-86.7%).

Additionally, the median progression-free survival (PFS) among these patients was 19.6 months (95% CI, 16.9-22.1), after a median follow-up of 19.4 months. Among those who received prior BTK and BCL-2 inhibition (n = 100), the median PFS was 16.8 months (95% CI, 13.2-18.7) and for those who received a BTK inhibitor but no prior BCL-2 inhibition, it was 22.1 months (95% CI, 19.6-27.4). The 12- and 18-month overall survival (OS) rates among the efficacy evaluable population was 86.0% (95% CI, 81.0%-89.8%) and 80.5% (95% CI, 74.8%-85.0%) after a median follow-up of 22.6 months.

“This is a major milestone for patients across Canada who are in urgent need of new treatment options," Mathilde Merlet, president and general manager of Lilly Canada, said in the news release.¹ "Our team has been committed to making [pirtobrutinib] available for Canadian patients with MCL and CLL/SLL, and we look forward to building on this milestone by advancing treatment options for people with hematologic malignancies."

The phase 1/2 BRUIN trial enrolled patients with relapsed/refractory B-cell lymphomas and treated them with 25 mg to 300 mg of pirtobrutinib once daily for each 28-day cycle in the phase 1 portion of the trial. They were treated with the recommended phase 2 dose of 200 mg in the phase 2 portion of the trial.

Those enrolled were a median age of 69 years (range, 36-88), 68.0% were male, and 99.6% had CLL. Most patients had Rai stage 0 to II disease (53.0%), an ECOG performance status of 0 (53.8%), and discontinued prior BTK inhibition due to disease progression (76.9%). The median number of prior lines of therapy was 3 (range, 1-11), with 47.0% of patients having received 4 or more prior lines.

The primary end point of the study was ORR by the 2018 International Workshop on Chronic Lymphocytic Leukemia response criteria. Secondary end points included overall response including PR with lymphocytosis, PFS, OS, and safety. An exploratory end point included an analysis for biomarkers.

The most common adverse effects (AEs) among 317 patients treated with pirtobrutinib in the safety population across all B-cell malignancies included fatigue (31.5%), diarrhea (26.5%), contusion (24.3%), cough (24.3%), and COVID-19 infection (24.0%). Common grade 3 AEs included anemia (8.8%), COVID-19 infection (5.0%), fatigue (1.9%). The common any-grade treatment-related AEs (TRAEs) included contusion (16.4%), diarrhea (8.8%), and headache (5.4%), with the most common grade 3 or higher event being anemia (2.2%).

TRAEs of special interest included bleeding (23.7%), bruising (19.6%), neutropenia (19.6%), and infections (12.3%). Additionally, the most common grade 3 or higher TRAEs of special interest included neutropenia (14.8%) and infections (3.8%). No drug-related ventricular fibrillation or ventricular tachycardia were observed in the trial.

MCL Population

Regarding the MCL cohort, results from the phase 1/2 BRUIN trial were published in the Journal of Clinical Oncology.³ Therein, among 90 patients previously treated for MCL with BTK inhibition, the objective response rate (ORR) per independent review committee (IRC) was 57.8% (95% CI, 46.9%-68.1%), with 20% of patients achieving a CR and 37.8% attaining a PR. Additionally, at a median follow-up of 12 months, the median DOR per IRC was 21.6 months (95% CI, 7.5-not reached [NR]), with estimated 6-, 12-, and 18-month rates of 73.6% (95% CI, 58.0%-84.2%), 57.1% (95% CI, 39.3%-71.5%), and 52.4% (95% CI, 33.9%-67.9%), respectively.

In this cohort, the median PFS by IRC was 7.4 months (95% CI, 5.3-12.5) and the median OS was NR (95% CI, 14.8-NR). The estimated 12- and 18-month OS rates were 67.6% (95% CI, 55.7%-77.0%) and 59.3% (95% CI, 46.1%-70.2%), respectively.

In the primary efficacy cohort, the median age was 70 years (range, 46-87 years). The median prior number of lines was 3 (range, 1-8), and 77.8% of patients had intermediate- or high-risk disease based on simplified MCL International Prognostic score. Additionally, 82.2% of patients discontinued prior covalent BTK inhibition due to disease progression.

The safety profile of patients with MCL was consistent with patients treated across all B-cell malignancies. TEAEs resulting in treatment discontinuation occurred in 9.1% of patients, including 3.0% experienced drug-related discontinuations. A total of 11 grade 5 TEAEs were observed, none of which were related to study treatment.

Based on results from the phase 3 BRUIN-CLL-321 trial (NCT04666038), the FDA granted traditional approval to pirtobrutinib monotherapy for in the same patient population in December 2025.⁴ Additionally, pirtobrutinib was granted accelerated approval in 2023 as a treatment for patients with relapsed/refractory MCL previously given 2 prior lines of therapy, including a BTK inhibitor.⁵

References

1. Jaypirca® (pirtobrutinib), the first and only non-covalent (reversible) BTK inhibitor, now available in Canada for adult patients with relapsed or refractory mantle cell lymphoma and chronic lymphocytic leukemia. News release. Eli Lilly Canada. January 27, 2026. Accessed January 27, 2026. https://tinyurl.com/dzprxz9m
2. Mato AR, Woyach JA, Brown JR, et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;391(1):33-44. doi: 10.1056/NEJMoa2300696
3. Wang ML, Jurczak W, Zinzani PL, et al. Pirtobrutinib in covalent Bruton tyrosine kinase inhibitor pretreated mantle-cell lymphoma. J Clin Oncol. 2023;41(24):3988-3997. doi:10.1200/JCO.23.00562
4. FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma. News release. FDA. December 3, 2025. Accessed January 27, 2026. https://tinyurl.com/3tyaw463
5. FDA grants accelerated approval to pirtobrutinib for relapsed or refractory mantle cell lymphoma. News release. FDA. January 27, 2023. Accessed January 27, 2026. https://tinyurl.com/46vum4ns