The Food and Drug Administration (FDA) has recently announced the Priority Review of “odronextamab to treat adult patients with relapsed/refractory follicular lymphoma or relapsed/refractory diffuse large B-cell lymphoma (DLBCL), who have progressed after at least two prior systemic therapies.” Priority Review means that the FDA aims to take action on a drug application within six months, compared to 10 months under standard review. This accelerated review is supported by data from the phase 1 ELM-1 and the phase 2 ELM-2 trial. March 31, 2024 is the FDA target decision date for the possible approval of odronextamab.

Odronextamab is an off-the-shelf CD20×CD3 bispecific antibody, meaning that it binds to a cell surface protein called CD3 on T cells and CD20 on B cells, triggering T‐cell‐mediated cell death of the cancerous DLBCL cells. This drug is given intravenously. 

Positive Results So Far

• In the Phase 1 ELM-1 study, odronextamab given by itself showed a manageable safety profile and encouraging antitumor activity, including durable responses in heavily pretreated patients with DLBCL
• In the Phase 2 ELM-2 study, patients with relapsed/refractory DLBCL who had not received CAR T-cell therapy had an objective response rate (ORR) of 49% and a complete response (CR) rate of 31%. The median duration of complete response was 18 months 
• In the Phase 2 ELM-2 study, for patients who had received prior CAR-T therapy, 48% ORR was achieved and 32% CR was reached
• Odronextamab has shown encouraging activity when used at doses >80mg for patients before or after CAR-T treatment

Odronextamab Side Effects

Safety among patients has also been evaluated. Some of the adverse effects were as follows:

• 56.5% experienced cytokine release syndrome (CRS), an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction, that is associated with chimeric antigen receptor (CAR)-T cell therapy, therapeutic antibodies, and haploidentical allogeneic transplantation
• 40% experienced neutropenia, lower than normal neutrophils in your body 
• 31% experienced a high fever
• Anemia occurred in 30%
• Joint stiffness and diarrhea occurred in 21%
• 20% experienced a low platelet count

An Encouraging Future

"The Phase 1 and pivotal Phase 2 odronextamab data demonstrated deep and durable responses that were consistent in patients who progress after CAR-T therapy, which is important as they have particularly difficult-to-treat disease and no effective treatment options. Coupled with its overall safety profile, these clinically important results reinforce the potential of odronextamab to treat this aggressive blood cancer."

The ELM-1 and ELM-2 studies are still ongoing. Regeneron, the pharmaceutical company developing odronextamab, states that they are also initiating a broad Phase 3 development program to investigate odronextamab in earlier lines of therapy and other types of non-Hodgkin lymphomas, representing one of the largest clinical programs in lymphoma.