a study of pirtobrutinib (loxo-305) versus ibrutinib in participants with chronic lymphocytic leukemia (cll)/small lymphocytic lymphoma (sll)

Conditions: Chronic Lymphocytic Leukemia; Leukemia, Lymphocytic; Leukemia, B-cell; Small Lymphocytic Lymphoma

Summary: the purpose of part 1 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. the purpose of part 2 of this study evaluates pirtobrutinib monotherapy in treatment-naïve participants with cll/sll with 17p deletions. participation could last up to six years for part 1. participation could last up to 2 years for part 2.


Eligibility criteria:
inclusion 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) exclusion criteria: * 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). part 2: participants must be treatment naïve * 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

Keywords: btki hematologic disease lymphoma, non-hodgkin's lymphoma, b-cell