Eli Lilly and Company (NYSE: LLY) today announced it will present data from two pivotal Phase 3 studies reinforcing the efficacy of Jaypirca (pirtobrutinib) in treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The findings, drawn from the BRUIN CLL-314 and BRUIN CLL-313 trials, are set to be showcased at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, from December 6-9, 2025.
The data marks a significant milestone in Lilly’s oncology strategy, potentially positioning Jaypirca a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor as a formidable contender in earlier lines of treatment, including for patients who have never received prior therapy.
Head-to-Head Victory Against Ibrutinib
In a major development for the competitive BTK inhibitor landscape, Lilly will share results from BRUIN CLL-314, an open-label, randomized Phase 3 trial comparing Jaypirca directly against Imbruvica (ibrutinib), the first-generation covalent BTK inhibitor.
The study met its primary endpoint of non-inferiority in overall response rate (ORR). Notably, the data indicated that Jaypirca not only matched the standard of care but showed a response rate favoring Jaypirca with a nominal p-value for superiority of <0.05. While progression-free survival (PFS) data remains immature, early trends reportedly favor Jaypirca.
This study is particularly consequential as it is the first head-to-head Phase 3 trial against a covalent BTK inhibitor to include treatment-naïve patients, potentially challenging the dominance of established therapies in the first-line setting.
“Striking” First-Line Results
Lilly will also present late-breaking data from the BRUIN CLL-313 study, which evaluated Jaypirca against standard chemoimmunotherapy (bendamustine plus rituximab) in patients with treatment-naïve CLL/SLL without the 17p deletion.
The trial met its primary endpoint, demonstrating a “highly statistically significant and clinically meaningful” improvement in progression-free survival (PFS). While overall survival (OS) data is not yet fully mature, Lilly reports it is “trending strongly” in favor of Jaypirca.
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The results from BRUIN CLL-313 are striking and provocative, across both PFS and OS endpoints,
With this third positive Phase 3 study, we continue to build the clinical evidence supporting the possible role of pirtobrutinib in a variety of CLL/SLL treatment settings, including treatment-naïve, BTK inhibitor-naïve, and BTK inhibitor-exposed patients.
Jacob Van Naarden
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Expanding the Clinical Footprint
Currently, Jaypirca holds accelerated approval in the U.S. for patients with CLL/SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor, as well as for relapsed or refractory mantle cell lymphoma (MCL).
The new data sets form the backbone of Lilly’s strategy to expand Jaypirca’s label into earlier lines of therapy. By demonstrating superiority over chemoimmunotherapy and non-inferiority (with potential superiority) against ibrutinib, Lilly aims to offer a new standard of care that addresses the limitations of existing covalent BTK inhibitors, such as resistance and tolerability issues.
The detailed results from both studies will be part of the official press program at the ASH Annual Meeting, highlighting their anticipated impact on clinical practice.
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