Odronextamab Receives FDA Priority Review in R/R DLBCL/Follicular Lymphoma

The European Medicines Agency accepted a marketing authorization application for odronextamab for relapsed/refractory follicular lymphoma or DLBCL in August 2023.

The FDA has granted priority review to a biologics license application (BLA) for odronextamab as a treatment for patients diagnosed with relapsed/refractory follicular lymphoma or diffuse large B-cell lymphoma (DLBCL) following progression on 2 or more previous systemic therapies, according to a press release from Regeneron Pharmaceuticals.¹

The CD20xCD3 bispecific antibody was designed to bridge CD20 on cancer cells via CD3-expressing T cells, resulting in localized T-cell activation and cancer cell death. The BLA is supported by findings from 2 studies: the phase 1 ELM-1 trial (NCT02290951), and the phase 2 ELM-2 trial (NCT03888105).

The ELM-1 study assessed the safety and tolerability of odronextamab in a population diagnosed with CD20-positive B-cell malignancies, including non-Hodgkin lymphoma and chronic lymphocytic leukemia. The trial has 2 parts, with part A including a dose escalation and expansion phase via an intravenous administration, and part B including a dose finding and dose expansion phase for subcutaneous administration.

The study has an estimated enrollment of 200 patients. To be included on the study, patients were required to have at least 1 bi-dimensionally measurable lesion of 1.5 cm or more, an ECOG performance status of 0 to 1, and a life expectancy of 6 months or more. Patients with primary central nervous system (CNS) lymphoma or suspected CNS involvement were excluded. Additional exclusion criteria included receipt of standard anti-lymphoma chemotherapy or radiotherapy within 28 days of first study drug administration, as well as infection with the following:

• Human immunodeficiency virus,
• chronic hepatitis B,
• hepatitis C,
• or cytomegalovirus.

The ELM-2 trial assessed odronextamab in a population of patients with previously treated B-cell non-Hodgkin lymphoma, including those with follicular lymphoma, DLBCL, and mantle cell lymphoma. The study has an estimated enrollment of 512 patients.

To be included in the follicular lymphoma cohort, patients needed to have confirmed disease via central histopathologic testing and grade 1 to 3a disease. Those with grade 3b disease were instead included in the other B-cell non-Hodgkin lymphoma cohort. Additionally, those in the DLBCL cohort needed to have relapsed after or been refractory to a minimum of 2 previous lines of systemic therapy.

The phase 2 study included 121 patients with relapsed/refractory follicular lymphoma, 82% of whom experienced an objective response following treatment with odronextamab.² Investigators also reported a complete response (CR) rate of 75%. In the population of CAR T-cell therapy–naïve patients with relapsed/refractory DLBCL, the overall response rate was 49%, and the CR rate was 31% after treatment with the single agent.³

The European Medicines Agency accepted a marketing authorization application for odronextamab for relapsed/refractory follicular lymphoma or DLBCL in August 2023.⁴ The application was also supported by findings from the ELM-1 and ELM-2 studies.

References

1. Odronextamab BLA for treatment of relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) accepted for FDA priority review. News release. Regeneron Pharmaceuticals. September 29, 2023. Accessed September 29, 2023. https://bit.ly/3ZzBuJm
2. Odronextamab (CD20xCED3) demonstrates high and durable complete response rate among patients with relapsed/refractory follicular lymphoma in pivotal phase 2 trial. News release. Regeneron Pharmaceuticals. December 12, 2022. Accessed September 29, 2023. https://shorturl.at/myGLQ
3. Pivotal odronextamab (CD20xCD3) phase 2 data in patients with relapsed/refractory diffuse large B-cell lymphoma debut at ASH. News release. Regeneron Pharmaceuticals. December 11, 2022. Accessed September 29, 2023. https://shorturl.at/jLP59
4. Odronextamab receives EMA filing acceptance for treatment of relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. News release. Regeneron Pharmaceuticals. August 17, 2023. Accessed September 29, 2023. https://shorturl.at/qsBV0