A trial to learn how effective and safe odronextamab is compared to standard of care for adult participants with previously treated aggressive B-cell Non-Hodgkin Lymphoma.

Prior treatment

• Wash-out period from prior anti-lymphoma treatments and infections, as described in the protocol

Other illness

• History of or current relevant CNS pathology, as described in the protocol
• A malignancy other than NHL unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated
• Any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, as described in the protocol
• Allergy/hypersensitivity to study drug, or excipients.

Other

• Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL, as described in the protocol
• Other protocol defined exclusion criteria apply

• Histologically proven aggressive B-NHL, as described in the protocol. Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed.
• Have primary refractory or relapse 12 months or less (≤) from initiation of frontline therapy. Only patients who received 1 prior line of therapy containing an anti-Cluster of Differentiation 20 (CD20) antibody and anthracycline are allowed for enrollment
• Have measurable disease with at least one nodal lesion with longer diameter (LDi) greater than 1.5 cm or at least one extranodal lesion with LDi greater than 1.0 cm, documented by diagnostic imaging (computed tomography [CT] or magnetic resonance imaging [MRI])
• Intent to proceed to autologous stem cell transplant (ASCT), as described in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Adequate hematologic and organ function.
• Other protocol defined inclusion criteria apply