Pirtobrutinib

BRUIN CLL-322 is the first Phase 3 study to demonstrate superiority over a venetoclax-containing control arm in CLL, and, with the majority of patients previously treated with a covalent BTK inhibitor, reflects current practice patterns These data will be highlighted in a late-breaking oral presentation at the 2026 European Hematology Association (EHA) Annual Meeting June 14, 2026 -- Eli Lilly and Company (NYSE: LLY) today announced results from the Phase 3 BRUIN CLL-322 clinical trial of Jaypirca (pirtobrutinib), a non-covalent 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). The study met its primary endpoint of independent review committee (IRC)-assessed progression-free survival (PFS), demonstrating that the addition of pirtobrutinib to a two-year venetoclax plus rituximab regimen reduced the risk of disease progression or death by 45% (HR=0.55 [95% CI, 0.40-0.75]; p=0.0001). These data will be highlighted in a late-breaking oral presentation at the 2026 European Hematology Association (EHA) Annual Meeting taking place in Stockholm, Sweden, as well as featured in the meeting's press program. "These results from BRUIN CLL-322 show that the addition of pirtobrutinib as part of a time-limited regimen further enhanced an already effective treatment and extended the duration of remission for patients with previously treated CLL. Importantly, the study provides the first robust evidence for such an approach in patients who received a prior BTK inhibitor," said Matthew S. Davids, M.D., M.M.Sc., Chief of the Division of Lymphoma at Dana-Farber Cancer Institute, who is the lead author on the study. "Time-limited regimens are an important option in CLL care and provide patients with meaningful treatment-free intervals. In the context of the modern CLL treatment landscape, where many patients may only receive two lines of therapy, these results speak to the potential benefits that improving second-line therapy can have. Our study has the potential to establish a new standard of care in this population." BRUIN CLL-322 enrolled 639 relapsed or refractory patients, with 79.8% having prior covalent BTK inhibitor exposure, who were randomized 1:1 to receive pirtobrutinib plus venetoclax and rituximab (PVR, n=321) or venetoclax and rituximab alone (VR, n=318). Patients in the PVR arm received three cycles of pirtobrutinib and the first three cycles of rituximab before venetoclax was introduced. The efficacy results are based on a Feb. 2, 2026 data cutoff. At a median follow-up of 27.3 months, the primary endpoint of IRC-assessed PFS was significantly improved with the addition of pirtobrutinib to VR compared to VR alone (HR=0.55 [95% CI, 0.40-0.75]; p=0.0001). Median PFS in the PVR arm was not reached (95% CI, 43.3-NE), versus 39.7 months (95% CI, 35.9-NE) in the VR arm. The PFS results were consistent across prespecified subgroups, including patients with prior covalent BTK inhibitor exposure (PVR: not reached [95% CI, 41.5-NE] versus VR: 36.2 months [95% CI, 33.2-NE]), those who discontinued prior covalent BTK inhibitor due to progressive disease (PVR: 43.3 months [95% CI, 39.2-NE] versus VR: 33.2 months [95% CI, 28.3-37.5]), as well as those with high-risk features such as unmutated IGHV, TP53 mutation and/or 17p deletion, and/or complex karyotype. In an exploratory analysis of second-line patients whose disease progressed after a first-line covalent BTK inhibitor, the median PFS was not reached (95% CI, 30.1-NE) in the PVR arm and was 28.3 months (95% CI, 20.5-NE) in the VR arm (HR=0.32 [95% CI, 0.14-0.73]), with 24-month PFS rates of 88% (95% CI, 75.7-94.6) and 52% (95% CI, 34.7-66.2), respectively, and consistent benefit was observed regardless of the specific prior covalent BTK inhibitor received. Overall survival (OS), a key secondary endpoint, was not yet mature at this analysis (HR=0.89 [95% CI, 0.57-1.40]), and final testing of OS superiority is planned at a future date. An additional secondary endpoint, time to next treatment (TTNT), consistently favored the pirtobrutinib combination regimen (HR=0.50 [95% CI, 0.35-0.70]; nominal p<0.0001). 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, TTNT, event-free survival, overall response rate, time to worsening of CLL/SLL-related symptoms, time to worsening of physical functioning, safety and tolerability. 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 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. 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 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 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 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 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 The content above comes from the network. if any infringement, please contact us to modify.