Phase III BRUIN CLL-313 Trial Finds Jaypirca Extends Progression-Free Survival in Treatment-Naïve CLL/SLL

Eli Lilly has shared positive results from the Phase III BRUIN CLL-313 clinical trial (NCT05023980) evaluating Jaypirca (pirtobrutinib) versus chemoimmunotherapy (bendamustine plus rituximab) in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) without 17p deletions.¹

Positive topline results for PFS and OS

Topline data show that treatment with Jaypirca demonstrated a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus bendamustine and rituximab, meeting the study’s primary endpoint.

Lilly also provided an update on one of the trial’s key secondary endpoints, overall survival (OS). While not yet mature at the time of this this readout, it is trending strongly in favor of treatment with Jaypirca.

Results from this analysis of Jaypirca, a non-covalent (reversible) Bruton tyrosine kinase (BTK) inhibitor, indicate one of the most compelling effect sizes ever observed for a single agent BTK inhibitor in a front-line CLL study.

In a press release, Jacob Van Naarden, executive vice president and president of Lilly Oncology, said: "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. With this third positive Phase III 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."

Context from other BRUIN trials

In combination with encouraging data from the Phase III BRUIN CLL-314 study (NCT05254743)—the first-ever head-to-head Phase III trial versus ibrutinib in CLL to include treatment-naïve patients—results from this readout of BRUIN CLL-313 will form the basis for potential label expansion with regulatory submissions expected to begin later this year.

Phase III BRUIN CLL-313 clinical trial design

The BRUIN CLL-313 trial is a global, randomized, open-label study.

• The study enrolled 282 patients randomized 1:1 to receive either pirtobrutinib 200 mg orally once daily or bendamustine plus rituximab at labeled doses.
• Bendamustine plus rituximab is a standard chemoimmunotherapy regimen for chronic lymphocytic leukemia.
• The primary endpoint was PFS, assessed by an independent review committee.
• Secondary endpoints included overall response rate (ORR) by investigator and independent review, duration of response (DoR), OS, time to next treatment, safety and tolerability, and patient-reported outcomes.

Earlier FDA approval of Jaypirca

In December 2023, Jaypirca was approved by the FDA for the treatment of adult patients with CLL/SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. The approval was based on positive ORR and DOR data from the open-label, single-arm, multicohort, international, Phase I/II BRUIN trial (NCT03740529).²

Results from BRUIN showed:

• Among 108 patients with CLL/SLL enrolled in the trial, ORR was 72%, which were all partial responses.
• Median time to response was observed at 3.7 months, with a median DOR of 12.2 months.

In a press release from the time of the approval, William G. Wierda, MD, PhD, professor, medical director, and CLL section head for the Department of Leukemia at The University of Texas MD Anderson Cancer Center, said: "Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients. Jaypirca offers a new treatment option and different approach to targeting BTK, providing clinical benefit for a high proportion of patients with CLL or SLL in the BRUIN Phase I/II trial whose disease progressed following treatment with a covalent BTK inhibitor and with a BCL-2 inhibitor."

References

1. Lilly's Jaypirca (pirtobrutinib), the first and only approved non-covalent (reversible) BTK inhibitor, significantly improved progression-free survival in patients with treatment-naïve CLL/SLL. News release. Eli Lilly. September 8, 2025. Accessed September 11, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-jaypirca-pirtobrutinib-first-and-only-approved-non-0

2. Jaypirca® (pirtobrutinib) Now Approved by U.S. FDA for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Who Have Received at Least Two Lines of Therapy, Including a BTK Inhibitor and a BCL-2 Inhibitor. News release. Eli Lilly. December 1, 2023. Accessed September 11, 2025. https://investor.lilly.com/news-releases/news-release-details/jaypircar-pirtobrutinib-now-approved-us-fda-treatment-adult