A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN-CLL-314)
Summary
The purpose of Part 1 of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL; participants may or may not have already had treatment for their cancer. The purpose of Part 2 of this study evaluates pirtobrutinib monotherapy in treatment-naïve participants with CLL/SLL with 17p deletions. Participation could last up to six years for Part 1. Participation could last up to 2 years for Part 2.
Arms & interventions
- DrugPirtobrutinib
Administered orally.
- DrugIbrutinib
Administered orally.
Outcome measures
Primary
Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (Cri), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Part 1
ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
Time frame: Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest] (approximately 3 years and 5 months)
Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (CRi), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Part 2
ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
Time frame: Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest (Approximately 2 years and 3 months)
Secondary
IRC-assessed Progression-Free Survival (PFS)
Time frame: Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months)
Investigator assessed Progression-Free Survival (PFS)
Time frame: Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months)
Event-Free Survival (EFS)
Time frame: Randomization to first occurrence of treatment discontinuation due to adverse event/toxicity, treatment-emergent atrial fibrillation or atrial flutter of any grade, progressive disease (PD) or death (approximately 4 years)
Duration of Response (DOR)
Time frame: Time from the date of the first documented response of CR, CRi, nPR or PR to the earlier of documentation of definitive PD (per iwCLL 2018 criteria) or death from any cause (approximately 2 years)
Overall Survival (OS)
Time frame: Randomization to death from any cause (approximately 6 years)
Time to Next Treatment (TTNT)
Time frame: Randomization to initiation of the next systemic anticancer therapy for CLL/SLL or death from any cause, whichever occurs first (approximately 6 years)
Time to Worsening (TTW) of CLL/SLL Related Symptoms
Time frame: Randomization to time to worsening symptoms (approximately 4 years)
Comparative Tolerability
Time frame: From Baseline to Treatment Discontinuation for Any Reason (approximately 4 years)
Percentage of Participants Achieving DOR Part 2
Time frame: Time from the date of the first documented response of CR, CRi, nPR, or PR to the earlier of the documentation of definitive PD or death from any cause] (Approximately 2 years)
Eligibility criteria
Study locations (19)
Pacific Cancer Medical Center, Inc
Anaheim, California, 92801
TOI Clinical Research
Cerritos, California, 90703
Stanford School of Medicine-Cancer Clinical Trials Office
Palo Alto, California, 94305
California Cancer Associates for Research and Excellence
San Marcos, California, 92069
Florida Cancer Specialists
Fort Myers, Florida, 33916-2233
Cancer Specialists of North Florida -St Augustine
Saint Augustine, Florida, 32086
Florida Cancer Specialists East
West Palm Beach, Florida, 33401
Hematology Oncology Clinic
Baton Rouge, Louisiana, 70809
Tulane Cancer Center Office of Clinical Research
New Orleans, Louisiana, 70112
American Oncology Partners of Maryland, PA
Bethesda, Maryland, 20817
St. Vincent Frontier Cancer Center
Billings, Montana, 59102
Cancer Care Associates of York
York, Pennsylvania, 17403
Prisma Health Cancer Institute
Greenville, South Carolina, 29605
Sarah Cannon Research Institute SCRI
Nashville, Tennessee, 37203
Kelsey Research Foundation
Houston, Texas, 77025
Lumi Research
Kingwood, Texas, 77339
Virginia Cancer Institute
Richmond, Virginia, 23230
Medical Oncology Associates, PS
Spokane, Washington, 99208
MultiCare Health System Institute for Research and Innovation
Spokane, Washington, 99218
References
- Eyre TA, Hess LM, Masoudi E, Jen MH, Abhyankar S, Graham-Clarke PL, Bhandari NR, Maguire P, Winfree KB, Tracey M, Taipale KL, Davids MS. Efficacy of Pirtobrutinib Monotherapy in Treatment-Naive Chronic Lymphocytic Leukemia: A Bayesian Network Meta-Analysis of Randomized Controlled Trials. Cancers (Basel). 2026 Feb 18;18(4):660. doi: 10.3390/cancers18040660.(PubMed)
- Woyach JA, Qiu L, Grosicki S, Wrobel T, Capra M, Czyz J, Yi S, Eom KS, Panovska A, Jurczak W, Laribi K, Jacobasch L, Baker R, Agajanian R, Berkovits A, Ozcan M, Lepretre S, Coombs CC, Cramer P, Lewis KL, Hill M, Bao K, Bian Y, De Batista Ribeiro SR, Bhandari NR, Ruppert AS, Leow CC, Wierda WG. Pirtobrutinib Versus Ibrutinib in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. J Clin Oncol. 2026 Feb 20;44(6):476-485. doi: 10.1200/JCO-25-02477. Epub 2025 Dec 7.(PubMed)