Pitobrutinib/Pitobrutinib Outperforms Ibrutinib in Phase 3 Clinical Trial for CLL/SLL

Pirtobrutinib (Jaypirca; Eli Lilly) met the primary endpoint of overall response rate (ORR) in a head-to-head phase 3 trial compared with ibrutinib (Imbruvica; ibrutinib) in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL). Additionally, although premature, progression-free survival (PFS) data trended favorably, suggesting the potential efficacy of pitubrutinib in this treatment setting.

Pitobrutinib, formerly known as LOXO-305, is an oral, highly selective, non-covalent inhibitor of Bruton's tyrosine kinase (BTK), a molecular target found in many B-cell malignancies, including mantle cell lymphoma (MCL) and CLL/SLL. In 2023, it received accelerated approval from the U.S. Food and Drug Administration for adults with CLL/SLL who have received at least 2 prior therapies, including a BTK inhibitor and a BCL2 inhibitor. The decision was based on data from the BRUIN trial (NCT03740529), which showed an ORR of 72% and a duration of response (DOR) of 12.2 months in patients treated with pitubrutinib.

To further elucidate the efficacy and safety of pitubrutinib, this study was conducted in a head-to-head study of ibrutinib, the first BTK inhibitor approved by the U.S. Food and Drug Administration, which led to a complete change in the CLL/SLL treatment landscape. Notably, this trial is the first-ever head-to-head phase 3 study to include untreated patients (n=225).

BRUIN CLL-314 (NCT05254743) is a randomized, open-label study investigating pitubrutinib versus ibrutinib in patients with CLL/SLL who are either treatment-naïve or previously treated and naïve to BTK inhibitors. Patients (n=650) were randomized 1:1 to receive 200 mg of pitubrutinib orally once daily or 420 mg of ibrutinib orally once daily. The primary endpoint isORR, and key secondary endpoints include PFS, DOR, event-free survival, time to next treatment, overall survival, safety and tolerability. 1,5

Eli Lilly Oncology launches pitubrutinibA randomized development program that includes an ambitious series of clinical trials, including head-to-head studies against modern standards of care, as well as examination of patient populations that reflect real-world use, such as patients pretreated with BTK inhibitors. These data mark the second active Phase 3 study in the program as evidence continues to build support for pitubrutinib's potential role in treating patients with CLL/SLL, with the hope of future regulatory approval allowing physicians to use the drug in a variety of disease settings, either untreated or pre-treated with a BTK inhibitor.

References:https://www.pharmacytimes.com/view/pirtobrutinib-outperforms-ibrutinib-in-head-to-head-phase-3-trial-for-cll-sll