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)

• Status: Recruiting
• Trial end date: 2027-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Loxo Oncology, Inc.
• Treatments: Rituximab; Venetoclax

Criteria

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 and/or strong P-glycoprotein (P-gp) inhibitors

• 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