Eli Lilly's Jaypirca Cuts Risk Of CLL Progression Or Death By 80% In Phase 3 Trial

Eli Lilly and Company (NYSE:LLY) today announced results from the Phase 3 BRUIN CLL-313 clinical trial of Jaypirca (pirtobrutinib), a non-covalent Bruton tyrosine kinase (BTK) inhibitor, versus bendamustine plus rituximab (BR), in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) without 17p deletions. Pirtobrutinib met its primary endpoint demonstrating a reduction in the risk of disease progression or death by 80% (HR=0.20 [95% CI, 0.11-0.37]; p<0.0001).

 

These data will be highlighted in a late-breaking oral presentation at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in Orlando, Florida and simultaneously published in the Journal of Clinical Oncology.

"The results from BRUIN CLL-313 show a significant effect size, among the most pronounced ever observed for a single agent BTK inhibitor in a front-line CLL study," said Wojciech Jurczak, MD, PhD, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland. "The magnitude of the progression-free survival benefit, early overall survival trend and safety profile observed in BRUIN CLL-313 offer highly compelling evidence for the potential role of pirtobrutinib in treatment-naïve CLL."

BRUIN CLL-313 is the first prospective, randomized Phase 3 study examining the efficacy and safety of a non-covalent BTK inhibitor, pirtobrutinib, exclusively in patients with treatment-naïve CLL/SLL. BRUIN CLL-313 enrolled 282 patients with previously untreated CLL/SLL without del(17p), who were randomized 1:1 to receive continuous pirtobrutinib monotherapy (n=141) or BR (n=141). Crossover to the pirtobrutinib arm was allowed after independent review committee (IRC)-confirmed disease progression. The efficacy results are based on a July 11, 2025, data cutoff.

At a median follow-up of 28.1 months, the primary endpoint of IRC-assessed progression-free survival (PFS) was significantly improved with pirtobrutinib compared to BR (HR=0.20 [95% CI, 0.11–0.37]; p<0.0001). PFS results favored pirtobrutinib across all pre‑specified subgroups, including those with high-risk molecular features such as TP53 mutations, complex karyotype, and unmutated IGHV, and was consistently observed among investigator assessments. 

Overall survival (OS), a key secondary endpoint, remains immature, but a trend favoring pirtobrutinib was observed (HR=0.257 [95% CI, 0.070–0.934]; p=0.0261) despite over half (52.9%) of patients treated with BR crossing over to receive pirtobrutinib after IRC-confirmed disease progression. Final testing of OS superiority is planned at a future date.

The overall safety profile of patients treated with pirtobrutinib in BRUIN CLL-313 was similar to previously reported trials. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 40.0% of patients who received pirtobrutinib versus 67.4% with BR. Fewer adverse event-related dose reductions (3.6% versus 31.1%) and TEAE-related discontinuations (4.3% versus 15.2%) were seen with pirtobrutinib versus BR. The incidence of all-grade and high-grade atrial fibrillation/flutter were similar between pirtobrutinib and BR, a notable finding as BR is not a regimen associated with increased risk of this side effect (1.4% versus 1.5% and 0.7% versus 0.8%, respectively).

"These findings support the potential use of pirtobrutinib in certain treatment-naïve patients and underscore its unique position as the only BTK inhibitor to show promise in treating both newly diagnosed patients with CLL or SLL and those who have progressed on a covalent BTK inhibitor," said Jacob Van Naarden, executive vice president and president, Lilly Oncology. "Alongside the recently presented BRUIN-CLL 314 results, we are excited about how collectively these data may advance the therapeutic landscape in treatment-naïve CLL and are hopeful we will receive regulatory approvals for pirtobrutinib in earlier disease settings sometime next year, further expanding treatment options for patients."

Lilly has begun submitting results from BRUIN CLL-313 and BRUIN CLL-314 studies to regulatory authorities with the goal of further expanding Jaypirca's label into earlier lines of therapy.

Lilly is studying Jaypirca in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.