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Indianapolis, IN – august 4, 2025 – Eli Lilly and Company announced today positive topline results from the Phase 3 BRUIN CLL-314 trial, demonstrating that pirtobrutinib (Jaypirca) significantly improved progression-free survival (PFS) compared to ibrutinib (imbruvica) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This marks the second accomplished Phase 3 trial for the non-covalent bruton’s tyrosine kinase (BTK) inhibitor, bolstering its potential as a treatment option for heavily pretreated patients.
Pirtobrutinib is indicated for adult patients with mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a BTK inhibitor, and for adults with CLL or SLL who have had at least two prior lines of therapy, including both a BTK inhibitor and a BCL-2 inhibitor. The BRUIN CLL-314 trial specifically focused on patients who had progressed after treatment with ibrutinib,a first-generation covalent BTK inhibitor.
These findings build upon the results of the previously published Phase 3 BRUIN-321 trial, detailed in the Journal of Clinical Oncology in June 2025. That study, led by researchers including Dr. John P. Sharman at the University of Washington Medical Center in Seattle, WA, compared pirtobrutinib to investigator’s choice of idelalisib/rituximab or bendamustine/rituximab in patients relapsed or refractory to a covalent BTK inhibitor. The BRUIN-321 trial showed a median PFS of 14 months (95% CI, 11.2-16.6) for pirtobrutinib versus 8.7 months (95% CI, 8.1-10.4) for the control arm. Moreover, patients receiving pirtobrutinib experienced fewer grade 3 or higher treatment-emergent adverse events and a lower rate of treatment discontinuation due to adverse events.
Pirtobrutinib distinguishes itself from earlier BTK inhibitors like ibrutinib thru its non-covalent binding mechanism. This allows it to inhibit BTK more effectively, even in the presence of mutations that can confer resistance to covalent inhibitors. BTK is a crucial signaling molecule in B cells, and its inhibition disrupts the survival and proliferation of malignant cells in CLL and MCL.
According to eli Lilly, the safety profile observed in BRUIN CLL-314 was consistent with previous clinical trials. Detailed data from the trial will be presented at an upcoming medical conference later this year.
“These data mark the second positive phase 3 study in the programme, as we continue to build evidence supporting the potential role of pirtobrutinib in treating people with CLL/SLL and hopefully enabling future regulatory approvals that allow physicians to use the medicine in various disease settings, whether treatment-naive or BTK inhibitor-pretreated,” stated Dr. Maura van Naarden, a Lilly executive.
References
1. Lilly’s Jaypirca (pirtobrutinib), the first and only approved non-covalent (reversible) BTK inhibitor, met its primary endpoint in a head-to-head Phase 3 trial versus Imbruvica (ibrutinib) in CLL/SLL. News release. Eli Lilly. July 29, 2025. Accessed August 4, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-jaypirca-pirtobrutinib-first-and-only-approved-non
2. Sharman JP, Munir T, Grosicki S, et al. Phase III Trial of pirtobrutinib versus idelalisib/rituximab or bendamustine/rituximab in covalent Brut