A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (BRUIN CLL-322)

Loxo Oncology

Status and phase: Active, not recruiting; Phase 3

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: Venetoclax; Drug: Rituximab; Drug: Pirtobrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04965493

LOXO-BTK-20022

J2N-OX-JZNO (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to compare the efficacy and safety of fixed duration pirtobruitinib (LOXO-305) with VR (Arm A) compared to VR alone (Arm B) in patients with CLL/SLL who have been previously treated with at least one prior line of therapy. Participation could last up to five years.

Enrollment: 600 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
• Previous treatment with at least one line of therapy that may include a covalent Bruton's tyrosine kinase (BTK) inhibitor
• Platelets greater than or equal to (≥)50 x 10⁹/liter (L), hemoglobin ≥8 grams/deciliter (g/dL) and absolute neutrophil count ≥1.0 x 10⁹/L
• Adequate organ function
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

Exclusion criteria

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

• Prior therapy with a non-covalent (reversible) BTK inhibitor

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

• Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers

• Prior therapy with venetoclax

• Central nervous system (CNS) involvement

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

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

• Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within 60 days

• Active hepatitis B or hepatitis C

• Known active cytomegalovirus (CMV) infection

• Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA)

• Significant cardiovascular disease

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

• Patients with the following hypersensitivity:

  • Known hypersensitivity to any component or excipient of pirtobrutinib and venetoclax
  • Prior significant hypersensitivity to rituximab
  • Known allergy to allopurinol and inability to take uric acid lowering agent

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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600 participants in 2 patient groups

Arm A (PVR)

Experimental group

Description:

Fixed duration pirtobrutinib in combination with venetoclax and rituximab

Treatment:

Drug: Pirtobrutinib

Drug: Rituximab

Drug: Venetoclax

Arm B (VR)

Active Comparator group

Description:

Venetoclax with rituximab

Treatment:

Drug: Rituximab

Drug: Venetoclax