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BRUIN CLL-322 is the first Phase 3 readout in CLL to utilize and outperform a venetoclax-containing control arm
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This trial predominantly enrolled a patient population previously treated with covalent BTK inhibitors, highly relevant to current practice
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These results mark the fourth positive Phase 3 study of pirtobrutinib in CLL
INDIANAPOLIS, April 13, 2026 /PRNewswire/ --Eli Lilly and Company(NYSE: LLY) today announced positive topline results from the Phase 3 BRUIN CLL-322 trial of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton tyrosine kinase (BTK) inhibitor, plus venetoclax and rituximab versus venetoclax and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). Treatment in both study arms was administered for up to two years, after which patients do not take any CLL therapy until their disease progresses. The study met its primary endpoint, demonstrating that the addition of pirtobrutinib to venetoclax plus rituximab led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS), as assessed by an independent review committee (IRC). Results were consistent across clinically relevant subgroups and regardless of whether patients were previously treated with a covalent BTK inhibitor.
Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis, but was trending in favor of the pirtobrutinib combination regimen. The overall safety profile of this regimen was consistent with the known safety profile of each medicine. Rates of adverse events were similar across the study arms, with low rates of treatment regimen discontinuations, also similar between arms.
Detailed results will be presented at a medical congress and submitted to a peer-reviewed journal. Lilly intends to submit these results to regulators later this year for a label expansion.
"BRUIN CLL-322 was an ambitious trial, building on an effective regimen, and these results outperformed our expectations," saidJacob Van Naarden, executive vice president and president of Lilly Oncology. "Modern CLL treatment regimens provide such durable disease control that the vast majority of patients see their entire disease course managed by only one or two lines of therapy. For doctors and patients who prefer a time-limited approach, these BRUIN CLL-322 data demonstrate that the addition of Jaypirca could further extend the duration of benefit in second line CLL. Together with the other Phase 3 data recently published from the BRUIN clinical program, these data reinforce the potential role that pirtobrutinib may have, whether as a time-limited combination as a second line treatment or as a continuously dosed monotherapy in either line of therapy. We look forward to sharing the detailed data later this year and pursuing regulatory approvals to enable broad access."
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, 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, and the BRUIN CLL-313 trial, the first prospective, randomized Phase 3 study to examine the efficacy and safety of a non-covalent BTK inhibitor exclusively in patients with treatment-naïve CLL. For more information on the BRUIN Phase 3 clinical trial program, please visit clinicaltrials.gov.
About BRUIN CLL-322
BRUIN CLL-322 is a global, randomized, open-label, Phase 3 study comparing time-limited pirtobrutinib plus venetoclax and rituximab versus venetoclax and rituximab in previously treated CLL/SLL patients. The trial enrolled 639 patients, who were randomized 1:1 to receive pirtobrutinib (200 mg, once daily) plus venetoclax and rituximab per their labeled doses or venetoclax and rituximab alone. The primary endpoint is PFS as assessed by blinded IRC. Secondary endpoints include PFS as assessed by investigator, OS, time to next treatment, event-free survival, overall response rate, time to worsening of CLL/SLL-related symptoms, time to worsening of physical functioning, safety and tolerability.
About Jaypirca (pirtobrutinib)
Jaypirca (pirtobrutinib) (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 & 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