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

Eligibility Criteria

• * Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
• * Part 1 - Known 17p deletion status (wildtype or deleted). Part 2 - Must have deletion of 17p as determined by FISH testing
• * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• * Adequate organ function
• * 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,
• * Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis
• * Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis
• * Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min)
• * Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment
• * Known or suspected central nervous system (CNS) involvement
• * A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease
• * Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia \[AIHA\], idiopathic thrombocytopenic purpura \[ITP\])
• * Significant cardiovascular disease including ejection fraction \< 40% and any grade ongoing atrial fibrillation or atrial flutter
• * Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests
• * Active cytomegalovirus (CMV) infection
• * Active uncontrolled systemic bacterial, viral, or fungal infection
• * Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
• * Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments
• * Ongoing inflammatory bowel disease
• * Previous treatment for CLL/SLL - Part 1: Treatment-naïve and previously treated, except prior exposure to BTK inhibitor (covalent or noncovalent).
• * Concurrent use of investigational agent or anticancer therapy except hormonal therapy
• * Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
• * Use of \> 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug
• * Vaccination with a live vaccine within 28 days prior to randomization
• * 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
• * Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib