Pirtobrutinib versus ibrutinib for people with CLL or SLL.

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Pacific Cancer Medical Center, Inc
  Anaheim, California, United States Recruiting
• TOI Clinical Research
  Cerritos, California, United States Recruiting
• Stanford School of Medicine-Cancer Clinical Trials Office
  Palo Alto, California, United States Recruiting
• Florida Cancer Specialists
  Fort Myers, Florida, United States Recruiting
• Cancer Specialists of North Florida -St Augustine
  Saint Augustine, Florida, United States Recruiting
• Florida Cancer Specialists East
  West Palm Beach, Florida, United States Recruiting

+93 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
• Email: LillyTrials@Lilly.com
• Phone: 1-317-615-4559

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• NX-5948 vs Pirtobrutinib in R/R CLL/SLL

  This study tests NX-5948 against pirtobrutinib in people with relapsed or refractory CLL/SLL who have previously tried a covalent BTK inhibitor.

  Recruiting at 6 sites Phase 3 Nurix Therapeutics, Inc. · Macon, Georgia and 5 other locations · NCT07516093

• Comparing a BTK-targeted protein degrader (BGB-16673) with pirtobrutinib for adults with relapsed or refractory CLL or SLL

  This trial tests whether BGB-16673 works better and is as safe as pirtobrutinib for adults whose CLL or SLL has come back or not responded after prior covalent BTK inhibitor treatment.

  Recruiting at 217 sites Phase 3 BeOne Medicines · Birmingham, Alabama and 216 other locations · NCT06973187

• Evaluating Pirtobrutinib for patients with relapsed or refractory CLL/SLL

  This study is testing a new medication called Pirtobrutinib to see if it helps people with relapsed or hard-to-treat chronic lymphocytic leukemia or small lymphocytic lymphoma feel better after they’ve already tried other treatments.

  Recruiting at 125 sites Phase 2 Eli Lilly and Company · Chandler, Arizona and 128 other locations · NCT06588478

• Combining pirtobrutinib and venetoclax for treating resistant CLL or SLL

  This study is testing if combining two drugs, pirtobrutinib and venetoclax, can help people with chronic lymphocytic leukemia or small lymphocytic lymphoma that hasn’t responded to previous treatments.

  Recruiting Phase 2 Ohio State University Comprehensive Cancer Center · Columbus, Ohio · NCT06466122

• Fixed-duration treatment for chronic lymphocytic leukemia with pirtobrutinib and obinutuzumab

  This study is testing a year-long treatment combining two medications, pirtobrutinib and obinutuzumab, to see if it helps people with chronic lymphocytic leukemia feel better.

  Recruiting at 4 sites Phase 2 Dana-Farber Cancer Institute · Scarborough, Maine and 3 other locations · NCT06333262

• Comparing Nemtabrutinib to Ibrutinib or Acalabrutinib for First Line Treatment of Chronic Lymphocytic Leukemia

  This study is testing if a new drug called nemtabrutinib works as well as or better than two existing treatments for people with chronic lymphocytic leukemia who haven’t had treatment before.

  Recruiting at 181 sites Phase 3 Merck Sharp & Dohme LLC · Mobile, Alabama and 205 other locations · NCT06136559

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.