Pirtobrutinib met the primary endpoint of response rate non-inferiority, favoring pirtobrutinib with a nominal P-value for superiority < 0.05
Progression-free survival data was immature, but trending in favor of pirtobrutinib
BRUIN CLL-314 is the first-ever head-to-head Phase 3 study versus a covalent BTK inhibitor to include treatment-naïve patients
Eli Lilly and Company (NYSE: LLY) today announced positive topline results from the Phase 3 BRUIN CLL-314 clinical trial of Jaypirca (pirtobrutinib), a non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, versus Imbruvica (ibrutinib), a covalent BTK inhibitor, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). This study enrolled patients with treatment-naïve CLL/SLL and those who had been previously treated but were BTK inhibitor-naïve. The study met its primary endpoint of non-inferiority on overall response rate (ORR) as assessed by an independent review committee (IRC) in both the pre-treated and intent-to-treat populations. ORR favored pirtobrutinib with a nominal P-value for superiority1 (p <0.05). Progression free survival (PFS), a key secondary endpoint, was not yet mature at this analysis, but was trending in favor of pirtobrutinib. A formal PFS analysis testing for superiority is planned at a future analysis. No detriment was observed for overall survival (OS).
BRUIN CLL-314 is the first ever head-to-head trial versus ibrutinib in CLL to include treatment-naïve patients. This important subpopulation (n=225) had the longest follow-up and a particularly pronounced PFS effect size in favor of pirtobrutinib.
The overall safety profile of pirtobrutinib in BRUIN CLL-314 was similar to previously reported trials. Detailed results will be presented at a medical congress later in 2025.
“We launched the pirtobrutinib randomized development program with an ambitious suite of clinical trials, including head-to-head studies against modern standards of care and examinations of patient populations that reflect real world use, such as BTK inhibitor-pretreated patients,” said Jacob Van Naarden, executive vice president and president of Lilly Oncology. “These data mark the second positive Phase 3 study in the program, 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-naïve or BTK inhibitor-pretreated.”
These data build on the previously reported positive results from the BRUIN Phase 1/2 trial and the Phase 3 BRUIN CLL-321 trial, the first randomized, controlled study ever conducted in an exclusively post-covalent BTK inhibitor population. The BRUIN CLL-313 Phase 3 study of pirtobrutinib versus chemoimmunotherapy in treatment naïve CLL/SLL is expected to read out later in 2025 and combined with the results of BRUIN CLL-314, will form the basis of regulatory submissions globally. For more information on the BRUIN Phase 3 clinical trial program, please visit clinicaltrials.gov.
