Lilly announces promising results for Pirtobrutinib Phase 1/2 trials

Eli Lilly’s oncology arm, Loxo@Lilly, disclosed that The New England Journal of Medicine (NEJM) has published an extensive analysis of results from the BRUIN Phase 1/2 trials on pirtobrutinib, a reversible Bruton’s tyrosine kinase (BTK) inhibitor.

Pirtobrutinib is being investigated for use in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received BTK inhibitor therapy.

The detailed results, provided by NEJM, supplement the data set presented at the American Society of Hematology (ASH) Annual Meeting in 2022. This included a total of 247 CLL/SLL patients previously treated with BTK inhibitors, enrolled in both the Phase 1 and Phase 2 sections of the BRUIN study. The majority of patients discontinued their prior BTKi therapy due to disease progression (77%).

The publication also offered an in-depth examination of high-risk molecular features present in the majority of patients. These include del(17p) and/or TP53 mutation (47%), complex karyotype (42%), and unmutated IGHV (85%).

Lilly reports promising results for Phase 1/2 trials of BTK inhibitor Pirtobrutinib. Photo courtesy of Momoneymoproblemz/Wikimedia Commons.

David Hyman — Loxo@Lilly chief medical officer said: “We are pleased to have the detailed safety and efficacy results of pirtobrutinib in adults with CLL or SLL published in NEJM and shared with the broader medical community.

“Treating clinicians have expressed the desire to fully exhaust BTK inhibition prior to switching their patients to another therapy class. These data continue to reinforce pirtobrutinib’s ability to help reestablish BTK inhibition following treatment with a covalent BTK inhibitor.”

The main objective of the trial was to evaluate the overall response rate (ORR), inclusive of partial response (PR) or better, based on the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) response criteria. Other trial endpoints included progression-free survival (PFS), overall survival (OS), safety, and exploratory analyses of biomarkers.

For the subgroup of patients not previously treated with a BCL2 inhibitor (n=147), the ORR was 84.4% and the median PFS stood at 22.1 months. From all the patients who received at least one dose of pirtobrutinib (n=317), safety results indicated the most frequent treatment-emergent adverse events (TEAEs) were infections (71.0%), bleeding (42.6%), and neutropenia (32.5%). Notably, 87.4% of patients received at least one dose of pirtobrutinib at the recommended Phase 2 dose of 200 mg once daily.

Loxo@Lilly continues to study pirtobrutinib’s potential in CLL/SLL through numerous Phase 3 studies. The ongoing BRUIN Phase 1/2 clinical trial serves as the first global evaluation of pirtobrutinib in patients who were previously treated for mantle cell lymphoma (MCL), CLL, SLL, or other non-Hodgkin lymphomas (NHL).

Pirtobrutinib, a highly selective and reversible inhibitor of the enzyme BTK, was granted approval under the FDA’s Accelerated Approval pathway as Jaypirca (pirtobrutinib) on January 27, 2023. The drug is indicated for the treatment of adult patients with relapsed or refractory MCL after at least two lines of systemic therapy, including a BTK inhibitor.