Odronextamab Earns European Approval in R/R Follicular Lymphoma, DLBCL

"The [European Commission] approval of [odronextamab] is a meaningful advancement for patients [in the European Union] and their physicians as a new option to treat both indolent and aggressive lymphomas," according to Stefano Luminari, MD.

The European Commission has approved odronextamab (Ordspono) as a treatment for adults with relapsed/refractory follicular lymphoma or diffuse large B-cell lymphoma (DLBCL) following at least 2 prior lines of therapy, according to a press release from the developer, Regeneron Pharmaceuticals, Inc.¹

Previously, the European Medicine Agency’s Committee for Medicinal Products for Human Use issued a positive opinion supporting the approval of odronextamab in June 2024.² This regulatory decision represents the first approval of odronextamab in this indication.

“The [European Commission] approval of [odronextamab] is a meaningful advancement for patients [in the European Union] and their physicians as a new option to treat both indolent and aggressive lymphomas. In clinical trials, [odronextamab] demonstrated remarkable complete response [CR] rates in follicular lymphoma, as well as compelling efficacy results in [DLBCL], including in the post–CAR-T setting,” Stefano Luminari, MD, a professor of oncology at the University of Modena and Reggio Emilia and a hematologist in the Hematology Unit of Arcispedale Santa Maria Nuova in Reggio Emilia, stated in the press release.¹ “Physicians, especially in the community setting, will have an off-the-shelf option that can be administered out-patient—offering the chance for complete remission.”

Supporting data for the approval came from the phase 2 ELM-2 trial (NCT03888105) as well as the phase 1 ELM-1 trial (NCT02290951).

ELM-2 Trial

Based on independent review committee assessment, the objective response rate (ORR) with odronextamab was 80% among evaluable patients with follicular lymphoma (n = 128), which included CRs in 73%. The median duration of response (DOR) among those with a CR was 25 months (95% CI, 20-not estimable [NE]).

In a cohort of patients with DLBCL who had no prior CAR T-cell therapy (n = 127), treatment yielded an ORR of 52%. Additionally, the CR rate was 31%. Among patients with a CR, data showed a median DOR of 18 months (95% CI, 10-NE).

Additional findings published in Annals of Oncology showed a median progression-free survival (PFS) of 20.7 months (95% CI, 17.2-27.5) following treatment with odronextamab.³ The PFS rates were 66.2% at 12 months, 57.5% at 18 months, and 46.1% at 24 months. Additionally, the median overall survival (OS) was not reached (95% CI, 32.4-NE), with 12-month and 24-month OS rates of 86.2% and 70.1%, respectively.

In the open-label, multicohort ELM-2 trial, patients with relapsed/refractory B-cell non-Hodgkin lymphoma received odronextamab intravenously in 21-day cycles; investigators administered step-up dosing in the first cycle to help manage the risk of cytokine release syndrome (CRS).

ELM-1 Trial

Among 60 patients with DLBCL and disease progression following prior CAR T-cell therapy, independent review committee assessment indicated an ORR of 48%. Additionally, 32% of patients had a CR, and the median DOR among those with a response (n = 29) was 15 months (95% CI, 3 months-NE).

Investigators of the open-label, multicenter, phase 1 ELM-1 trial assessed the safety and tolerability of odronextamab as a treatment for those with CD20-positive B-cell malignancies who have progressed on prior anti-CD20 therapy.

Pooled safety data from the ELM-1 and ELM-2 trials showed that common adverse effects (AEs) included CRS (54%), neutropenia (41%), pyrexia (39%), anemia (38%), thrombocytopenia (27%), and diarrhea (24%). Frequent serious AEs included CRS (14%), pneumonia (9%), and COVID-19 (9%).

“[Odronextamab] marks the first approval from our bispecific antibody platform, which we hope will increasingly contribute to our growing portfolio of practice-changing medicines for oncology and other diseases. Building upon this approval, we are excited about our OLYMPIA program, which includes multiple phase 3 trials investigating [odronextamab] as a monotherapy and in various combinations, in earlier lines of therapy,” George D. Yancopoulos, MD, PhD, board co-chair, president, and chief scientific officer at Regeneron, concluded.¹

References

1. Ordspono (odronextamab) approved in the European Union for the treatment of relapsed/refractory follicular lymphoma, and diffuse large B-cell lymphoma. News release. Regeneron Pharmaceuticals, Inc. August 26, 2024. Accessed August 26, 2024. https://tinyurl.com/yk7acc5k
2. Odronextamab recommended for EU approval by the CHMP to treat relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. News release. Regeneron Pharmaceuticals, Inc. June 28, 2024. Accessed August 26, 2024. https://tinyurl.com/3vjw876z
3. Kim TM, Taszner M, Novelli S, et al. Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma. Ann Oncol. Published online August 13, 2024. doi:10.1016/j.annonc.2024.08.2239