Eli Lilly and Company reports Phase 3 BRUIN CLL-322 results showing Jaypirca (pirtobrutinib) plus venetoclax-rituximab significantly improved progression-free survival in relapsed CLL/SLL, supporting a time-limited second-line regimen.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Eli Lilly and Company reported positive topline results from the Phase 3 BRUIN CLL-322 trial evaluating Jaypirca (pirtobrutinib) in combination with venetoclax and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). The time-limited triple regimen demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with venetoclax plus rituximab alone, meeting the study’s primary endpoint.
Benefit Consistent Across Subgroups
Treatment in both arms was administered for up to two years, after which patients discontinued therapy until disease progression. The PFS benefit was assessed by an independent review committee and remained consistent across clinically relevant subgroups, including patients previously treated with covalent Bruton tyrosine kinase (BTK) inhibitors.
Overall Survival Trending Favorably
Overall survival, a key secondary endpoint, was not mature at the time of analysis but showed a trend favoring the pirtobrutinib-based combination. The safety profile aligned with the known characteristics of each agent. Rates of adverse events and treatment discontinuations were low and comparable between the two study arms.
Regulatory Plans and Data Presentation
Lilly said detailed findings will be presented at an upcoming medical congress and submitted to a peer-reviewed journal. The company plans to submit the data to regulatory authorities later this year to support a potential label expansion.
Executive Perspective
Jacob Van Naarden, executive vice president and president of Lilly Oncology, said the BRUIN CLL-322 study built on an already effective regimen and exceeded expectations. He noted that many patients with CLL now experience durable disease control with one or two lines of therapy, and the addition of Jaypirca to a time-limited regimen may further extend benefit in the second-line setting. He added that findings from the broader BRUIN clinical program support pirtobrutinib both as a time-limited combination therapy and as continuously dosed monotherapy across treatment lines.
Broader BRUIN Clinical Program Context
These findings build on previously reported results from the BRUIN Phase 1/2 study and multiple Phase 3 trials across the program. These include BRUIN CLL-321, the first randomized controlled study conducted exclusively in patients previously treated with a covalent BTK inhibitor; BRUIN CLL-314, the first head-to-head Phase 3 trial versus ibrutinib to include treatment-naïve CLL patients; and BRUIN CLL-313, the first prospective randomized Phase 3 study evaluating a non-covalent BTK inhibitor exclusively in treatment-naïve CLL.
Trial Design and Endpoints
BRUIN CLL-322 (NCT04965493) is a global, randomized, open-label Phase 3 study enrolling 639 previously treated CLL/SLL patients. Participants were randomized 1:1 to receive pirtobrutinib 200 mg once daily plus venetoclax and rituximab, or venetoclax and rituximab alone. Secondary endpoints include investigator-assessed PFS, overall survival, time to next treatment, event-free survival, response rate, symptom progression, physical functioning, and safety.
About Jaypirca (Pirtobrutinib)
Jaypirca is a highly selective, non-covalent BTK inhibitor designed to reversibly block the BTK enzyme, a validated target across B-cell malignancies including CLL and mantle cell lymphoma. The therapy is currently approved in the United States as an oral once-daily treatment taken until disease progression or unacceptable toxicity.
Reference
About the Writer
Chikkula Pavan Kumar, PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.