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RecruitingInterventionalPhase 3

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)

NCT ID: NCT05254743Sponsor: Loxo Oncology, Inc.Last updated: 2026-06-17

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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria * Part 1 - Known 17p deletion status (wildtype or deleted). Part 2 - Must have deletion of 17p as determined by FISH testing * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * Adequate organ function * Platelets greater than or equal to ≥ 50 x 10⁹/liter (L) or ≥30 x 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis, * Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis * Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis * Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min) Exclusion Criteria: * Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment * Known or suspected central nervous system (CNS) involvement * A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease * Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia \[AIHA\], idiopathic thrombocytopenic purpura \[ITP\]) * Significant cardiovascular disease including ejection fraction \< 40% and any grade ongoing atrial fibrillation or atrial flutter * Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests * Active cytomegalovirus (CMV) infection * Active uncontrolled systemic bacterial, viral, or fungal infection * Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count * Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments * Ongoing inflammatory bowel disease * Previous treatment for CLL/SLL - Part 1: Treatment-naïve and previously treated, except prior exposure to BTK inhibitor (covalent or noncovalent). Part 2: participants must be treatment naïve * Concurrent use of investigational agent or anticancer therapy except hormonal therapy * Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist * Use of \> 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug * Vaccination with a live vaccine within 28 days prior to randomization * Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment * Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib

Study locations (19)

Pacific Cancer Medical Center, Inc

Anaheim, California, 92801

Recruiting
· Contact
Veena Charu · Principal Investigator

TOI Clinical Research

Cerritos, California, 90703

Recruiting
· Contact
MICHAEL DEL ROSARIO · Principal Investigator

Stanford School of Medicine-Cancer Clinical Trials Office

Palo Alto, California, 94305

Recruiting
· Contact
Bita Fakhri · Principal Investigator

California Cancer Associates for Research and Excellence

San Marcos, California, 92069

Active Not Recruiting

Florida Cancer Specialists

Fort Myers, Florida, 33916-2233

Recruiting
· Contact
Jennifer Cultrera · Principal Investigator

Cancer Specialists of North Florida -St Augustine

Saint Augustine, Florida, 32086

Recruiting
· Contact
Ayed Ayed · Principal Investigator

Florida Cancer Specialists East

West Palm Beach, Florida, 33401

Recruiting
· Contact
Shachar Peles · Principal Investigator

Hematology Oncology Clinic

Baton Rouge, Louisiana, 70809

Active Not Recruiting

Tulane Cancer Center Office of Clinical Research

New Orleans, Louisiana, 70112

Active Not Recruiting

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817

Recruiting
· Contact
Victor Priego · Principal Investigator

St. Vincent Frontier Cancer Center

Billings, Montana, 59102

Recruiting
· Contact
Patrick Cobb · Principal Investigator

Cancer Care Associates of York

York, Pennsylvania, 17403

Active Not Recruiting

Prisma Health Cancer Institute

Greenville, South Carolina, 29605

Active Not Recruiting

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, 37203

Recruiting
· Contact
Bertrand Anz III · Principal Investigator

Kelsey Research Foundation

Houston, Texas, 77025

Active Not Recruiting

Lumi Research

Kingwood, Texas, 77339

Recruiting
David Nguyen · Principal Investigator

Virginia Cancer Institute

Richmond, Virginia, 23230

Recruiting
· Contact
Yuvraj Choudhary · Principal Investigator

Medical Oncology Associates, PS

Spokane, Washington, 99208

Recruiting
· Contact
Arvind Chaudhry · Principal Investigator

MultiCare Health System Institute for Research and Innovation

Spokane, Washington, 99218

Active Not Recruiting

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)