Eli Lilly Jaypirca met its primary endpoint in head-to-head Phase 3 study versus Imbruvica

These data will be highlighted 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.

"These data from BRUIN CLL-314 are both novel and clinically significant, demonstrating an improved overall response rate and a favorable trend in progression-free survival outcomes with pirtobrutinib compared to ibrutinib across all populations, including treatment-naïve patients where covalent BTK inhibitors are a cornerstone of treatment," said Jennifer A. Woyach, M.D., professor, hematologist-oncologist, and Director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute . "BRUIN CLL-314 is the first randomized study to compare covalent and non-covalent BTK inhibitors and to directly compare any BTK inhibitors in the treatment-naïve setting, offering findings that are important for advancing the field and patient care. These efficacy results, along with pirtobrutinib's safety profile, offer strong evidence on the role of pirtobrutinib earlier in the treatment course for patients with CLL or SLL."

The BRUIN CLL-314 study enrolled 662 patients who were randomized to receive pirtobrutinib (n=331) or ibrutinib (n=331), with the ITT population consisting of 225 treatment-naïve and 437 relapsed/refractory patients. The efficacy results utilize a June 10, 2025, data cutoff date.

The study achieved its primary endpoint demonstrating that pirtobrutinib was statistically non-inferior to ibrutinib in independent review committee (IRC)-assessed ORR for the ITT population, and results numerically favored pirtobrutinib (87.0% [95% CI, 82.90-90.44] versus 78.5% [95% CI, 73.73-82.85]; nominal p = 0.0035). Additionally, ORR consistently favored pirtobrutinib versus ibrutinib across all populations evaluated, including relapsed/refractory and treatment-naïve, as well as across pre-specified subgroups such as patients with and without 17p deletions, IGHV status and complex karyotype.

PFS, a key secondary endpoint, was not yet mature at this analysis but was trending in favor of pirtobrutinib compared to ibrutinib in the ITT (HR=0.569 [95% CI, 0.388-0.834]), relapsed/refractory (HR=0.729 [95% CI, 0.471-1.128]), and treatment-naïve (HR=0.239 [95% CI, 0.098-0.586]) populations, with a median follow-up of 22.0 months, 18.4 months, and 22.5 months, respectively. Among all subgroups, the largest PFS effect size was observed in the treatment-naïve subgroup, which had the longest follow-up at this data cut, with a 76% reduction in the risk of disease progression or death. A formal PFS analysis testing for superiority is planned at a future analysis. There was no detriment in overall survival (OS) (HR=0.961 [95% CI, 0.55-1.69]) for the ITT population.

The overall safety profile for patients treated with pirtobrutinib in BRUIN CLL-314 was similar to previously reported trials, and the most common treatment-emergent adverse events were similar between arms.

"We are excited to share these compelling new findings for pirtobrutinib with the scientific community at ASH and in the Journal of Clinical Oncology," said Jacob Van Naarden, executive vice president and president, Lilly Oncology. "These data build on additional results from the BRUIN development program and the recent FDA approval for pirtobrutinib in the post-covalent BTK inhibitor setting to reinforce the medicine's potential to deliver meaningful benefit for people living with CLL or SLL across various disease settings."

As part of the Late-Breaking Abstract Session on Dec. 9, Lilly will also share results from the Phase 3 BRUIN CLL-313 study of pirtobrutinib versus chemoimmunotherapy in patients with treatment-naïve CLL/SLL without del(17p). These data were also selected to be highlighted as part of the ASH Annual Meeting press program session on Dec. 8.