The purpose of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL. Participants may or may not have already had treatment for their cancer. Participation could last up to six years.
Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Adequate organ function Platelets greater than or equal to (≥)50 x 10⁹/liter (L), hemoglobin ≥8 grams/deciliter (g/dL), and absolute neutrophil count ≥0.75 x 10⁹/L 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 Active hepatitis B or hepatitis C 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 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