LOXO-BTK-20022

• 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