A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Inclusion Criteria:

1. Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
3. Adequate organ function

1. Platelets greater than or equal to (≥)50 x 10⁹/liter (L) or ≥30 x 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis,
2. Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis
3. Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis
4. Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

Exclusion Criteria:

1. Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment
2. Known or suspected central nervous system (CNS) involvement
3. A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease
4. Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
5. Significant cardiovascular disease including ejection fraction < 40% and any grade ongoing atrial fibrillation or atrial flutter
6. Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests
7. Active cytomegalovirus (CMV) infection
8. Active uncontrolled systemic bacterial, viral, or fungal infection
9. Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
10. Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments
11. Ongoing inflammatory bowel disease
12. Prior exposure to BTK inhibitor (covalent or noncovalent)
13. Concurrent use of investigational agent or anticancer therapy except hormonal therapy
14. Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
15. Use of ≥ 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug
16. Vaccination with a live vaccine within 28 days prior to randomization
17. Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment
18. Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib