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:

• Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria

• Previous treatment with at least one line of therapy that may include a covalentBruton's tyrosine kinase (BTK) inhibitor

• Platelets greater than or equal to (≥)50 x 10⁹/liter (L), hemoglobin ≥8grams/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 Kantagonist

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

• 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 ofdifferentiation 4 (CD4) count

• Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-Twithin 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 andvenetoclax

• Prior significant hypersensitivity to rituximab

• Known allergy to allopurinol and inability to take uric acid lowering agent