Key Takeaways
- Jaypirca Shows Superior Overall Response Rate (ORR) to Imbruvica: In the Phase III BRUIN CLL-314 trial, Jaypirca (pirtobrutinib) achieved a statistically significant improvement in ORR compared to Imbruvica (ibrutinib) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
- Favorable Progression-Free Survival Trend in Treatment-Naïve Patients: While progression-free survival data were not yet mature, early analysis showed a positive trend for Jaypirca, particularly in treatment-naïve patients.
- Broad Potential in CLL/SLL Treatment: These latest results build on previous BRUIN trial data and support Jaypirca’s potential for broader regulatory approval in both newly diagnosed and previously treated CLL/SLL populations.
Results from the Phase III BRUIN CLL-314 trial (NCT05254743) showed that Eli Lilly’s Jaypirca (pirtobrutinib) outperformed Imbruvica (ibrutinib) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). According to the company, BRUIN CLL-314 was the first ever head-to-head trial versus Imbruvica in CLL that included treatment-naïve patients.1
How Does Jaypirca Compare to Imbruvica in CLL/SLL?
"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, EVP, president, Lilly Oncology, in a press release.
BRUIN CLL-314 Trial Design and Primary Endpoints
- The randomized, open-label BRUIN CLL-314 trial evaluated Jaypirca versus Imbruvica in 650 patients with CLL/SLL.
- Patients were randomly assigned in a 1:1 ratio to receive either once daily Jaypirca or Imbruvica.
- The primary endpoint of the trial was overall response rate (ORR) as assessed by blinded independent review committee (IRC).
- Key secondary endpoints included investigator and IRC assessed progression-free survival (PFS), duration of response, event-free survival, time to next treatment, overall survival (OS), safety and tolerability, and patient-reported outcomes.1,2
Topline Results
- Results showed that Jaypirca demonstrated an ORR that was favorable compared to Imbruvica, reaching nominal statistical significance (p<0.05).
- Additionally, PFS data were not mature at the time of this analysis but showed a favorable trend for Jaypirca, especially in patients who were treatment-naïve.
- No detriment was observed in OS.
- The full data readout is expected later this year.1
Broader Development Program
Lilly stated that the results add to earlier positive findings from the BRUIN Phase I/II trial (NCT03740529) and the Phase III BRUIN CLL-321 trial (NCT04666038), which was the first randomized, controlled trial conducted solely in patients previously treated with covalent Bruton tyrosine kinase (BTK) inhibitors.3,4
CLL/SLL Epidemiology
According to the American Cancer Society, CLL accounts for one-third of all new cases of leukemia in the United States and approximately 1% of all cancers overall. It is most common in older adults, with an average diagnosis age of 70 years, and it is extremely rare in patients under 40 years of age and in children, while being slightly more common in men than in women. By the end of 2025, it is estimated that there will be approximately 23,690 new cases of CLL and 4,460 deaths.5
According to the Lymphoma Research Foundation, around 19% of patients with a B‑cell lymphoma have CLL/SLL, making it the third most common type of B‑cell lymphoma. In 2020, there were approximately 207,463 people living with CLL in the United States.6
Current Indications and Future Outlook
Jaypirca is currently indicated for adults with relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy and in adults with CLL/SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. However, both indications are currently approved under accelerated approval based on response rate, requiring further proof of clinical benefit to maintain the approval.1
"These data mark the second positive Phase III 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,” concluded Van Naarden, in the press release.
References
- Lilly's Jaypirca (pirtobrutinib), the first and only approved non-covalent (reversible) BTK inhibitor, met its primary endpoint in a head-to-head Phase 3 trial versus Imbruvica (ibrutinib) in CLL/SLL. Lilly. July 29, 2025. Accessed July 29, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-jaypirca-pirtobrutinib-first-and-only-approved-non
- A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN-CLL-314). Clinicaltrials.gov. Accessed July 29, 2025. https://clinicaltrials.gov/study/NCT05254743?term=BRUIN%20CLL-314%20&rank=1
- A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL. Clinicaltrials.gov. Accessed July 29, 2025. https://clinicaltrials.gov/study/NCT03740529
- Study of LOXO-305 (Pirtobrutinib) Versus Investigator's Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN CLL-321). Clinicaltrials.gov. Accessed July 29, 2025. https://clinicaltrials.gov/study/NCT04666038
- Key Statistics for Chronic Lymphocytic Leukemia (CLL). American Cancer Society. Accessed July 29, 2025. https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/about/key-statistics.html
- Understanding Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). Lymphoma Research Foundation. Accessed July 29, 2025. https://lymphoma.org/wp-content/uploads/2024/04/LRF_Understanding-Lymphoma_2023-PART-4.pdf?utm_source=chatgpt.com
