Odronextamab

This study is researching an experimental drug called odronextamab, referred to as study drug, when used in combination with chemotherapy. The study is focused on patients with Diffuse Large B-cell Lymphoma (DLBCL) that have not been treated before (called "previously untreated"). Patients with DLBCL that have come back after treatment (called "relapsed"), or have not responded to treatment (called "refractory"), can also participate in this study. This study will be made up of Part 1A, Part 1B, and Part 2.The aim of Part 1A and Part 1B of the study is to see how safe and tolerable the study drug in combination with chemotherapy is and to determine the dose and schedule of the study drug to be combined with chemotherapy in Part 2 of the study. The aim of Part 2 of the study is to see how effective the combination of the study drug with chemotherapy is in comparison with the combination of rituximab (the comparator drug), and chemotherapy, the current standard of care treatment approved for DLBCL. Standard of care means the usual medication expected and used when receiving treatment for a condition. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug when combined with chemotherapy * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects) * The impact from the study drug on quality of life and ability to complete routine daily activities

This phase II trial tests how well odronextamab works before and after standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapy in treating patients with diffuse large B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR-T cell therapy is the SOC treatment most patients receive when other treatments have failed. CAR-T cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Odronextamab is a monoclonal antibody that is called bispecific, as it individually targets 2 cell proteins, CD20 and CD3. Proteins are part of each cell in the body, which work together like little machines for the cell to function. CD20 is a protein that is found on the surface of both normal B-cells and B-cells that make up certain cancers, like DLBCL. CD3 is a protein that is found on the surface of T cells. T-cells and normal B-cells are types of white blood cells in the body and are a part of the immune system that fights infections. Odronextamab is designed to help T-cells find and kill the B-cells including the cancer cells in DLBCL. Giving odronextamab before and after CAR T-cell therapy may improve response in patients with relapsed or refractory DLBCL.