EU’s EMA Accepts Application for Odronextamab in Follicular Lymphoma/DLBCL

"These positive pivotal phase 2 results investigating odronextamab in heavily pre-treated, relapsed/refractory follicular lymphoma patients showed deep and durable response—confirming earlier findings in this program—with the highest [CR] rates seen in this patient population to date," according to Tae Min Kim, MD, PhD.

The European Medicines Agency has accepted a marketing authorization application (MAA) for the investigational CD20xCD3 bispecific antibody odronextamab for adult patients with relapsed/refractory follicular lymphoma or diffuse large B-cell lymphoma (DLBCL) with disease progression following a minimum of 2 prior lines of therapy, according to a press release from Regeneron Pharmaceuticals, Inc.¹

Supporting data for the MAA came from the phase 1 ELM-1 trial (NCT02290951) and the phase 2 ELM-2 trial (NCT03888105), which investigators presented during at the 2022 American Society of Hematology (ASH) Annual Meeting.

Among 121 patients with relapsed/refractory follicular lymphoma enrolled on the phase 2 trial, the objective response rate (ORR) was 82%, which included a complete response (CR) in 75% of patients.² Additionally, the median duration of CR was 20.5 months (95% CI, 17.0-not evaluable [NE]). Investigators also reported a median progression-free survival (PFS) of 20 months (95% CI, 15-NE). The median overall survival (OS) was not reached (95% CI, NE-NE) among those treated with odronextamab.

Among 131 patients who were evaluable for safety in this cohort, the most common adverse effects (AEs) included cytokine release syndrome (CRS; 56.5%), neutropenia (40%), pyrexia (31%), anemia (30%), and infusion-related reaction (29%). Seventy-eight percent of patients experienced grade 3 or higher toxicities. Additionally, 11.5% of patients discontinued treatment due to AEs, and investigators observed 1 death each due to pneumonia, progressive multifocal leukoencephalopathy, and systemic mycosis.

“These positive pivotal phase 2 results investigating odronextamab in heavily pre-treated, relapsed/refractory follicular lymphoma patients showed deep and durable response—confirming earlier findings in this program—with the highest [CR] rates seen in this patient population to date,” investigator Tae Min Kim, MD, PhD, a professor in the Department of Internal Medicine at Seoul National University Hospital in Seoul, South Korea said in a press release at the time these data were presented.² “We look forward to seeing the data continue to mature.”

In a cohort of 130 CAR T–naïve patients with relapsed/refractory DLBCL who were included on the phase 2 trial, odronextamab elicited an ORR of 49%, which included CRs in 31%.³ Additionally, the median duration of CR was 18 months (95% CI, 10-NE). Among 31 patients who previously received CAR T-cell therapy and enrolled in the phase 1 trial’s dose expansion cohort, the ORR was 48%, and 32% of patients had a CR. The median duration of CR in this cohort was not reached (95% CI, 2-NE).

The most common AEs among 140 patients evaluable for safety in the phase 2 cohort included CRS (55%), anemia (42%), pyrexia (39%), and neutropenia (28%). Investigators reported that 10% of patients discontinued treatment due to AEs. Five deaths occurred due to pneumonia in 3 patients, COVID-19 in 1, and pseudomonal sepsis in another.

“People with [DLBCL have] a disease that often relapses and becomes more aggressive each time it returns, leaving doctors with a shrinking set of treatment options,” trial investigator Won Seog Kim, MD, PhD, a professor at Samsung Medical Center and the Division of Hematology-Oncology at Sungkyunkwan University, in Seoul, South Korea, said in a press release at the time these findings were presented.³

“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.”

Investigators of the ongoing phase 2 ELM-2 trial are evaluating odronextamab in more than 500 patients with different diseases including DLBCL, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma. The trial’s primary end point is ORR based on Lugano Classification, and secondary end points include CRs, PFS, OS, and quality of life.

In the ongoing, open-label phase 1 ELM-1 trial, investigators are assessing the safety and tolerability of odronextamab in those with CD20-positive B-cell malignancies who have received prior treatment with CD20-directed antibodies.

References

1. 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 August 18, 2023. https://shorturl.at/qsBV0
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 August 18, 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 August 18, 2023. https://shorturl.at/jLP59