Recruiting
Phase 3

Pirtobruitinib vs. Ibrutinib

Sponsor:

Loxo Oncology, Inc.

Code:

NCT05254743

Conditions

Chronic Lymphocytic Leukemia

Leukemia, Lymphocytic

Leukemia, B-cell

Small Lymphocytic Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pirtobrutinib

Ibrutinib

Study Details

Brief 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.

Conditions

Chronic Lymphocytic Leukemia

Leukemia, Lymphocytic

Leukemia, B-cell

Small Lymphocytic Lymphoma

Study ID

NCT05254743

Start date

Jul 22, 2022

Status verified date

Aug, 2026

Completion date

Jan, 2028

Anticipated

Primary completion date

Oct, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

737 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Pirtobrutinib Part 1

Participants will receive pirtobrutinib orally.

active comparator: Ibrutinib Part 1

Participants will receive ibrutinib orally.

experimental: Pirtobrutinib Part 2

Participants will receive pirtobrutinib orally.

Interventions

Pirtobrutinib

Administered orally.

Ibrutinib

Administered orally.

Primary outcome measure

  • 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 [ 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 [ 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) ]

Central Contacts and Locations

Central contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

1-317-615-4559LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

clinical_inquiry_hub@lilly.com

Locations

Pacific Cancer Medical Center, Inc

Recruiting

Anaheim, California, United States, 92801

Contacts

714-999-1465

Principal Investigator:

Veena Charu

TOI Clinical Research

Recruiting

Cerritos, California, United States, 90703

Contacts

562-693-4477

Principal Investigator:

MICHAEL DEL ROSARIO

Stanford School of Medicine-Cancer Clinical Trials Office

Recruiting

Palo Alto, California, United States, 94305

Contacts

650-498-6000

Principal Investigator:

Bita Fakhri

Florida Cancer Specialists

Recruiting

Fort Myers, Florida, United States, 33916-2233

Contacts

727-216-1143

Principal Investigator:

Jennifer Cultrera

Cancer Specialists of North Florida -St Augustine

Recruiting

Saint Augustine, Florida, United States, 32086

Contacts

904-538-4488

Principal Investigator:

Ayed Ayed

Florida Cancer Specialists East

Recruiting

West Palm Beach, Florida, United States, 33401

Contacts

561-366-4100

Principal Investigator:

Shachar Peles

American Oncology Partners of Maryland, PA

Recruiting

Bethesda, Maryland, United States, 20817

Contacts

301-571-0019

Principal Investigator:

Victor Priego

St. Vincent Frontier Cancer Center

Recruiting

Billings, Montana, United States, 59102

Contacts

406-238-6685

Principal Investigator:

Patrick Cobb

Sarah Cannon Research Institute SCRI

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

423-622-6212

Principal Investigator:

Bertrand Anz III

Lumi Research

Recruiting

Kingwood, Texas, United States, 77339

Contacts

(832) 553-3661 ext. 122

Principal Investigator:

David Nguyen

Virginia Cancer Institute

Recruiting

Richmond, Virginia, United States, 23230

Contacts

804-287-3000

Principal Investigator:

Yuvraj Choudhary

Medical Oncology Associates, PS

Recruiting

Spokane, Washington, United States, 99208

Contacts

509-462-2273

Principal Investigator:

Arvind Chaudhry

Hopital de L'Enfant Jesus

Recruiting

Québec, Canada, G1J 1Z4

Contacts

418-525-4444 ext. 0

Principal Investigator:

Robert Delage

More Information

Sponsor

Loxo Oncology, Inc.

Last update posted

Aug 17, 2026

Last verified

Aug, 2026

Keywords

  • BTKi
  • Hematologic Disease
  • Lymphoma, non-Hodgkin's
  • Lymphoma, B-cell

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Loxo Oncology, Inc. on 2026-08-17.