Eli Lilly’s Jaypirca reduces the risk of disease progression by 80% in first-line CLL trials

USA— Eli Lilly and Company has released findings from the Phase 3 BRUIN CLL-313 clinical trial evaluating Jaypirca (pirtobrutinib), a non-covalent Bruton tyrosine kinase (BTK) inhibitor.

The study compared the drug against bendamustine plus rituximab (BR) in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who had not received prior treatment and did not have 17p deletions.

The trial successfully achieved its primary endpoint by showing that pirtobrutinib reduced the risk of disease progression or death by 80%.

Researchers presented these results at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, while simultaneously publishing them in the Journal of Clinical Oncology.

Dr. Wojciech Jurczak from the Maria Sklodowska-Curie National Research Institute of Oncology in Krakow, Poland, highlighted the significance of these findings.

He noted that the results represent one of the most substantial effect sizes ever documented for a single-agent BTK inhibitor used as initial treatment for CLL.

The progression-free survival benefit, combined with early overall survival trends and a favorable safety profile, provides compelling evidence for pirtobrutinib’s potential role in treating newly diagnosed CLL patients.

BRUIN CLL-313 marks the first prospective, randomized Phase 3 study to examine a non-covalent BTK inhibitor exclusively in treatment-naïve CLL/SLL patients.

The trial enrolled 282 patients with previously untreated CLL/SLL without del(17p) and randomly assigned them to receive either continuous pirtobrutinib monotherapy or BR, with 141 patients in each group.

The study design permitted patients in the BR arm to switch to pirtobrutinib after confirmed disease progression, as determined by an independent review committee.

At a median follow-up of 28.1 months, based on a July 11, 2025, data cutoff, pirtobrutinib demonstrated significantly improved progression-free survival compared to BR.

The benefits extended across all pre-specified subgroups, including patients with high-risk features such as TP53 mutations, complex karyotype, and unmutated IGHV. Investigators consistently observed these positive outcomes in their assessments.

While overall survival data remains immature as a key secondary endpoint, researchers noted a favorable trend toward pirtobrutinib despite more than half of BR-treated patients (52.9%) crossing over to receive pirtobrutinib after disease progression.

The study team plans to conduct final testing of overall survival superiority at a future date.

The safety profile of pirtobrutinib in BRUIN CLL-313 aligned with previous trial reports. Grade 3 or higher treatment-emergent adverse events occurred in 40.0% of pirtobrutinib patients compared to 67.4% in the BR group.

Additionally, pirtobrutinib showed lower rates of dose reductions due to adverse events (3.6% versus 31.1%) and treatment discontinuations (4.3% versus 15.2%).

Notably, atrial fibrillation and flutter rates remained similar between both treatment arms at all severity levels.

Jacob Van Naarden, executive vice president and president of Lilly Oncology, emphasized that these findings establish pirtobrutinib as the only BTK inhibitor showing promise for both newly diagnosed and previously treated CLL/SLL patients.

Combined with recently presented BRUIN-CLL 314 results, these data may reshape the treatment landscape for newly diagnosed CLL patients.

Lilly anticipates regulatory approvals for pirtobrutinib in earlier disease settings next year and has begun submitting results from both studies to regulatory authorities.