Study of LOXO-305 (Pirtobrutinib) Versus Investigator's Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Inclusion Criteria:

• Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria.

• Previously treated with a covalent BTK inhibitor.

• Eastern Cooperative Oncology Group (ECOG) 0-2.

• Absolute neutrophil count ≥ 0.75 × 10^9/L without granulocyte-colony-stimulatingfactor support, or ≥ 0.50 × 10^9/L in patients with documented bone marrowinvolvement considered to impair hematopoiesis. Granulocyte-colony-stimulatingfactor support is permitted in patients with documented bone marrow involvement.

• Hemoglobin ≥ 8 g/dL or ≥ 6 g/dL in patients with documented bone marrow involvementconsidered to impair hematopoiesis. Transfusion support is permitted in patientswith bone marrow involvement.

• Platelets ≥ 50 × 10^9/L. If an investigator has chosen bendamustine/rituximab as theArm B treatment, platelets must be ≥ 75 × 10^9/L. Patients may enroll below thesethresholds if the Investigator determines the cytopenia is related to bone marrowinvolvement considered to impair hematopoiesis. Patients with a platelet count < 30x 10^9/L are excluded.

• AST and ALT ≤ 3.0 x upper limit of normal (ULN).

• Total bilirubin ≤ 1.5 x ULN.

• Estimated creatinine clearance of ≥ 30 mL/min.

Exclusion Criteria:

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

• Known or suspected history of central nervous system (CNS) involvement by CLL/SLL.

• Ongoing drug-induced liver injury.

• Active uncontrolled auto-immune cytopenia.

• Significant cardiovascular disease.

• History of allogeneic or stem cell transplantation (SCT) or chimeric antigenreceptor-modified T cells (CAR-T) therapy within the past 60 days.

• Active hepatitis B or hepatitis C.

• Known active cytomegalovirus (CMV) infection.

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

• Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count.

• Clinically significant active malabsorption syndrome or inflammatory bowel disease

• Prior exposure to 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.

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

• Patients with the following hypersensitivity:

1. Known hypersensitivity, including anaphylaxis, to any component or excipient ofLOXO-305. For patients planned to receive idelalisib, known hypersensitivity,including anaphylaxis, to any component or excipient of idelalisib. Forpatients planned to receive bendamustine, known hypersensitivity, includinganaphylaxis, to any component or excipient of bendamustine.

2. Prior significant hypersensitivity to rituximab.