Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)

Inclusion Criteria:

• 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 stimulatingfactor support within 7 days of screening

• Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 7days of screening

• Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 7days 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 Criteria:

• 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 antigenreceptor 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 2/3consecutive ECGs, and mean QTcF>470 ms on all 3 ECGs

• Known HIV infection or active HBV, HCV, or CMV infections. (Certain participantswith controlled HBV infections may still be eligible)

• Clinically significant active malabsorption syndrome or other condition likely toaffect gastrointestinal (GI) absorption

• Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors orinducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitortherapy prior to start of study drug treatment.

• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin Kantagonist.

• Vaccination with live vaccine within 28 days prior to randomization