A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN-CLL-313)

Loxo Oncology

Status and phase: Active, not recruiting; Phase 3

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: Bendamustine; Drug: Pirtobrutinib; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05023980

18088

LOXO-BTK-20023

2024-511599-33-00 (EU Trial (CTIS) Number)

J2N-OX-JZNP (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to compare the efficacy and safety of pirtobrutinib (LOXO-305; Arm A) compared to BR (Arm B) in patients with CLL/SLL who have not been treated. Participation could last up to five years.

Enrollment: 282 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed diagnosis of CLL/SLL requiring therapy, per iwCLL 2018 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Adequate organ function
• Platelets greater than or equal to (≥)75 x 10⁹/liter (L) (≥50 × 10⁹/L for patients with evidence of bone marrow infiltrate), hemoglobin ≥8 grams/deciliter (g/dL), and absolute neutrophil count ≥0.75 x 10⁹/L
• Kidney function: Estimated creatinine clearance ≥40 milliliters per minute (mL/min)

Exclusion criteria

• Known or suspected Richter's transformation at any time preceding enrollment

• Prior systemic therapy for CLL/SLL

• Presence of 17p deletion

• Central nervous system (CNS) involvement

• Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])

• Significant cardiovascular disease

• Active hepatitis B or hepatitis C

• Active cytomegalovirus (CMV) infection

• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection

• Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count

• Concurrent use of investigational agent or anticancer therapy except hormonal therapy

• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist

• Vaccination with a live vaccine within 28 days prior to randomization

• Patients with the following hypersensitivity:

  • Known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or bendamustine
  • Prior significant hypersensitivity to rituximab

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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282 participants in 2 patient groups

Arm A - Pirtobrutinib

Experimental group

Description:

Participants received pirtobrutinib 200 milligrams (mg) orally once daily in continuous 28-day cycles until disease progression or unacceptable toxicity.

Treatment:

Drug: Pirtobrutinib

Arm B - Bendamustine Plus Rituximab

Active Comparator group

Description:

Participants received bendamustine 90 milligrams per square meter (mg/m²) intravenously on Days 1 and 2 of each 28-day cycle (Cycles 1-6) plus rituximab 375 mg/m² intravenously on Cycle 1 Day 1, then 500 mg/m² on Day 1 of Cycles 2-6. Eligible participants in Arm B crossed over to receive pirtobrutinib following independent review committee (IRC)-confirmed progressive disease (PD).

Treatment:

Drug: Rituximab

Drug: Bendamustine