Eli Lilly announces BRUIN CLL-314 clinical trial meets primary endpoint

Eli Lilly (LLY) announced results from the Phase 3 BRUIN CLL-314 clinical trial of Jaypirca, a non-covalent Bruton’s tyrosine kinase inhibitor, versus Imbruvica, a covalent BTK inhibitor, in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. This study enrolled patients with treatment-naive CLL/SLL and those who had been previously treated but were BTK inhibitor-naive. The study met its primary endpoint of non-inferiority on overall response rate as assessed by an independent review committee in both the pre-treated and intent-to-treat populations. ORR favored pirtobrutinib with a nominal P-value for superiority. Progression free survival, 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. BRUIN CLL-314 is the first ever head-to-head trial versus ibrutinib in CLL to include treatment-naive patients. This subpopulation 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. 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 naive 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.