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)

Inclusion Criteria:

1. Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
2. Previous treatment with at least one line of therapy that may include a covalent Bruton's tyrosine kinase (BTK) inhibitor
3. 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
4. Adequate organ function
5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
6. Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

Exclusion Criteria:

1. Known or suspected Richter's transformation at any time preceding enrollment
2. Prior therapy with a non-covalent (reversible) BTK inhibitor
3. Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
4. Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers
5. Prior therapy with venetoclax
6. Central nervous system (CNS) involvement
7. Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
8. Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
9. Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within 60 days
10. Active hepatitis B or hepatitis C
11. Known active cytomegalovirus (CMV) infection
12. Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA)
13. Significant cardiovascular disease
14. Vaccination with a live vaccine within 28 days prior to randomization

Patients with the following hypersensitivity:

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