In the Phase 3 BRUIN CLL-313 study, treatment with pirtobrutinib demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival versus bendamustine plus rituximab, indicating one of the most compelling effect sizes ever observed for a single agent BTK inhibitor in a front-line CLL study
BRUIN CLL-313 is the third positive Phase 3 study from the pirtobrutinib development program in CLL
Results from BRUIN CLL-313 and BRUIN CLL-314 will form the basis for seeking label expansions in earlier lines of therapy, with global regulatory submissions beginning later this year
INDIANAPOLIS, Sept. 8, 2025 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced positive topline results from the Phase 3 BRUIN CLL-313 clinical trial of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton tyrosine kinase (BTK) inhibitor, versus chemoimmunotherapy (bendamustine plus rituximab), in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) without 17p deletions. The study met its primary endpoint, demonstrating a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemoimmunotherapy, as assessed by an independent review committee (IRC), indicating one of the most compelling effect sizes ever observed for a single agent BTK inhibitor in a front-line CLL study.
Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis, but was trending strongly in favor of pirtobrutinib and will be tested for statistical significance at the time of the primary OS analysis, which is anticipated to occur in 2026. The overall safety profile of pirtobrutinib in BRUIN CLL-313 was generally consistent with previously reported trials across treatment settings.
Detailed results will be presented at a medical congress and submitted to a peer-reviewed journal. The results from the BRUIN CLL-313 and BRUIN CLL-314 studies will form the basis for seeking label expansions in earlier lines of therapy, with global regulatory submissions beginning later this year.
"The results from BRUIN CLL-313 are striking and provocative, across both PFS and OS endpoints, further demonstrating the potential of pirtobrutinib to be a meaningful treatment option for people with untreated CLL/SLL," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "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. We look forward to presenting these data, as well as data from the recently announced positive BRUIN CLL-314 study, at upcoming medical meetings and preparing global regulatory submissions, with the goal of making pirtobrutinib an option for a wider group of patients who might benefit."
These data build on the previously reported positive results from the BRUIN Phase 1/2 trial, the Phase 3 BRUIN CLL-321 trial, the first randomized, controlled study ever conducted in an exclusively post-covalent BTK inhibitor population, and the Phase 3 BRUIN CLL-314 trial, the first-ever head-to-head Phase 3 trial versus ibrutinib in CLL to include treatment-naïve patients. For more information on the BRUIN Phase 3 clinical trial program, please visit clinicaltrials.gov.
About BRUIN CLL-313
BRUIN CLL-313 is a Phase 3, global, randomized, open-label study of pirtobrutinib versus chemoimmunotherapy (bendamustine plus rituximab) in people with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) without 17p deletions who have not been previously treated. The trial enrolled 282 patients who were randomized 1:1 to receive pirtobrutinib (200 mg orally, once daily) or bendamustine plus rituximab (BR) per labeled doses. BR is a chemoimmunotherapy regimen used in the treatment of CLL. The primary endpoint is progression-free survival (PFS) as assessed by blinded independent review committee (IRC). Secondary endpoints include investigator and IRC assessed overall response rate (ORR), duration of response (DoR), and PFS, overall survival (OS), time to next treatment (TTNT), safety and tolerability and patient-reported outcomes (PRO).
About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.1 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).2,3 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable.
Endnotes and References:
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Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901. doi:10.1016/S0140-6736(21)00224-5
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Hanel W, Epperla N. Emerging therapies in mantle cell lymphoma. J Hematol Oncol. 2020;13(1):79. Published 2020 Jun 17. doi:10.1186/s13045-020-00914-1
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Gu D, Tang H, Wu J, Li J, Miao Y. Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies. J Hematol Oncol. 2021;14(1):40. Published 2021 Mar 6. doi:10.1186/s13045-021-01049-7