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Pirtobrutinib versus ibrutinib for people with CLL or SLL.

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)

Phase 3 Interventional Eli Lilly and Company · NCT05254743

This trial will test whether pirtobrutinib works better or is safer than ibrutinib for adults with CLL/SLL, with a separate part that tries pirtobrutinib alone in treatment‑naïve patients who have a 17p deletion.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment662 (estimated)
Ages18 Years and up
SexAll
SponsorEli Lilly and Company Industry-sponsored
Drugs / interventionspirtobrutinib, ibrutinib, prednisone, pirtobruitinib
Locations144 sites (Anaheim, California and 143 other locations)
Trial IDNCT05254743 on ClinicalTrials.gov

What this trial studies

This is a randomized Phase 3 comparison of the non‑covalent BTK inhibitor pirtobrutinib versus the covalent BTK inhibitor ibrutinib in people with CLL/SLL, with participants who may be treatment‑naïve or previously treated. A second study part enrolls treatment‑naïve participants who have a 17p deletion to receive pirtobrutinib monotherapy. Key outcomes include measures of cancer control and safety over long‑term follow‑up. Participation can last up to six years for Part 1 and up to two years for Part 2, and enrolled participants must meet performance status and organ function criteria.

Who should consider this trial

Good fit: Adults with CLL or SLL who need therapy, have ECOG performance status 0–2, adequate organ function, and known 17p deletion status (Part 1 accepts any 17p status; Part 2 requires 17p deletion and treatment‑naïve disease).

Not a fit: Patients with suspected Richter's transformation, significant organ dysfunction, or blood count and kidney function below the study cutoffs are unlikely to qualify or benefit from participation.

Why it matters

Potential benefit: If successful, pirtobrutinib could provide an effective alternative BTK inhibitor with activity in some patients who do not respond to or cannot tolerate existing BTK inhibitors.

How similar studies have performed: Earlier‑phase trials have shown promising activity for pirtobrutinib, including responses in patients previously treated with covalent BTK inhibitors, while ibrutinib is an established effective therapy in CLL.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Anaheim, California and 143 other locations

+94 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Chronic Lymphocytic LeukemiaLeukemia, LymphocyticLeukemia, B-cellSmall Lymphocytic LymphomaBTKiHematologic DiseaseLymphoma, non-Hodgkin'sLymphoma, B-cell
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.