BRUIN-MCL-321: This study is evaluating the effectiveness of a targeted therapy (called LOXO-305) compared to other similar targeted therapies (including ibrutinib, acalabrutinib, and zanubrutinib) in people with mantle cell lymphomaA Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Naive Mantle Cell Lymphoma (BRUIN MCL-321)

Inclusion

• Confirmed MCL diagnosis
• Previously treated with at least one prior line of systemic therapy for MCL
• Measurable disease per Lugano criteria
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Absolute neutrophil count ≥ 0.75 × 109/L without granulocyte-colony stimulating factor support within 7 days of screening
• Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 7 days of screening
• Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 7 days of screening.
• AST and ALT ≤ 3.0 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN.
• Creatinine clearance of ≥ 30 mL/min according to Cockcroft/Gault Formula

Exclusion

• Prior treatment with an approved or investigational BTK inhibitor
• History of bleeding diathesis
• History of stroke or intracranial hemorrhage within 6 months of randomization
• History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor modified T-cell (CAR-T) therapy within 60 days of randomization
• Clinically significant cardiovascular disease
• Prolonged QT interval corrected using Fridericia's formula (QTcF) > 470 ms on 2/3 consecutive ECGs, and mean QTcF>470 ms on all 3 ECGs
• Known HIV infection or active HBV, HCV, or CMV infections. (Certain participants with controlled HBV infections may still be eligible)
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption
• Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment.
• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
• Vaccination with live vaccine within 28 days prior to randomization