Lilly Announces Positive Phase 3 Data for Jaypirca (Pirtobrutinib) with Over 90% Overall Response Rate in Treatment-Naïve CLL/SLL Patients

(Source:WuXi AppTec）

Source: WuXi AppTec

Today,Eli Lilly and Company inThe positive topline results of Jaypirca (pirtobrutinib) in the BRUIN CLL-314 Phase 3 clinical trial were disclosed in the abstract published at the American Society of Hematology (ASH) Annual Meeting. The study evaluated the efficacy and safety of pirtobrutinib for the treatment of patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).Notably, in treatment-naïve CLL/SLL patients, the overall response rate (ORR) in the pirtobrutinib group was as high as 92.9%!

Pirtobrutinib is a highly selective non-covalent Bruton's tyrosine kinase inhibitor (BTKi), which has previously demonstrated clear efficacy in CLL/SLL patients who have received prior covalent BTKi treatment.The data announced this time come from the first head-to-head comparison study between pirtobrutinib and ibrutinib, with participants including treatment-naïve patients and relapsed/refractory (R/R) patients who have not received covalent BTKi therapy. The data cutoff date for this analysis was June 10, 2025, encompassing the final ORR analysis for the intent-to-treat (ITT) and R/R populations, as well as preliminary results of secondary endpoints, including the treatment-naïve population. The study enrolled a total of 662 patients, randomized 1:1 to either the pirtobrutinib group (n=331) or the active control group (n=331). The median number of prior treatment lines in both groups was 1; the ITT population included 225 treatment-naïve patients and 437 R/R patients.

The results showed that the study met its primary endpoint.In the ITT population, the ORR for the pirtobrutinib group and the control group were 87.0% (95% CI: 82.9-90.4) and 78.6% (95% CI: 73.7-82.9), respectively, with a statistically significant difference (two-sided p<0.0001).In the R/R population, the ORR for the two groups was 84.0% (95% CI: 78.5-88.6) and 74.8% (95% CI: 68.5-80.4), respectively, also achieving statistical significance (two-sided p<0.0001).In the initial treatment population, the ORR for pirtobrutinib was 92.9% (95% CI: 86.4-96.9), compared to 85.8% (95% CI: 78.0-91.7) in the control group.

Further subgroup analysis showed,Pirtobrutinib demonstrated consistent efficacy advantages regardless of 17p deletion status.：In patients with 17p deletion, the ORR in ITT and R/R populations were 80.0% vs 75.0% and 80.6% vs 80.0%, respectively; in patients without 17p deletion, the ORR in ITT and R/R populations were 88.3% vs 79.2% and 84.7% vs 73.8%, respectively. Although progression-free survival (PFS) data are not yet mature, trends favoring pirtobrutinib were observed across ITT (HR=0.57, 95% CI: 0.39-0.83), R/R (HR=0.73, 95% CI: 0.47-1.13), and treatment-naïve populations (HR=0.24, 95% CI: 0.10-0.59), with median follow-up durations of 21.8 months, 18.2 months, and 22.5 months, respectively. The most common types of adverse events were similar between the two groups, and the safety profile was generally manageable.

References:

[1] Pirtobrutinib vs ibrutinib in treatment-naïve and relapsed/refractory CLL/SLL: Results from the first randomized phase III study comparing a non-covalent and covalent BTK inhibitor. Retrieved November 3, 2025 from https://meetings-api.hematology.org/api/abstract/vmpreview/291232

[2] A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN-CLL-314). Retrieved November 3, 2025 from https://clinicaltrials.gov/study/NCT05254743