A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN-CLL-314)

Loxo Oncology

Status and phase: Active, not recruiting; Phase 3

Conditions: Leukemia, B-cell; Small Lymphocytic Lymphoma; Leukemia, Lymphocytic; Chronic Lymphocytic Leukemia

Treatments: Drug: Pirtobrutinib; Drug: Ibrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05254743

J2N-OX-JZNU (Other Identifier)

2023-507699-38-00 (EU Trial (CTIS) Number)

18281

LOXO-BTK-20030 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 725 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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725 participants in 3 patient groups

Pirtobrutinib Part 1

Experimental group

Description:

Participants will receive pirtobrutinib orally.

Treatment:

Drug: Pirtobrutinib

Ibrutinib

Active Comparator group

Description:

Participants will receive ibrutinib orally.

Treatment:

Drug: Ibrutinib

Pirtobrutinib Part 2

Experimental group

Description:

Participants will receive pirtobrutinib orally.

Treatment:

Drug: Pirtobrutinib