EU Greenlights Odronextamab for R/R Follicular Lymphoma and DLBCL

The European Commission (EC) has approved odronextamab (Ordspono) for the treatment of adult patients with relapsed/refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) who have received at least 2 prior lines of systemic therapy.¹

This regulatory decision was supported by findings from the phase 1 ELM-1 (NCT02290951) and phase 2 ELM-2 (NCT03888105) trials. In ELM-2, among 128 patients with relapsed/refractory FL, the overall response rate (ORR) per independent review committee (IRC) was 80%, including a complete response (CR) rate of 73%. Among patients who achieved a CR, the median duration of response (DOR) was 25 months (95% CI, 20-not evaluable [NE]). In the same trial, among 127 patients with relapsed/refractory DLBCL who were CAR T-cell therapy–naive, the ORR per IRC was 52%, including a CR rate of 31%. Among patients who achieved a CR, the median DOR was 18 months (95% CI, 10-NE).

In ELM-1, among 60 patients with relapsed/refractory DLBCL who had progressed following CAR T-cell therapy, the ORR per IRC was 48%, including a CR rate of 32%. The median DOR among responders was 15 months (95% CI, 3-NE).

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

Across both trials, the most common adverse effects (AEs) were cytokine release syndrome (CRS; 54%), neutropenia (41%), pyrexia (39%), anemia (38%), thrombocytopenia (27%), diarrhea (24%), and COVID-19 (22%). The most common serious AEs were CRS (14%), COVID-19 (9%), pneumonia (9%), and pyrexia (6%). Odronextamab is associated with serious or fatal infections, as well as CRS that may be serious or life-threatening, according to the news release.

The ELM-1 Trial

The ongoing ELM-1 trial is evaluating odronextamab in patients with CD20-positive B-cell malignancies, including FL and DLBCL, who have previously received treatment with CD20-directed antibody therapy, including a cohort of patients with DLBCL who have progressed following CAR T-cell therapy.² Part B of the trial is investigating the agent administered subcutaneously in dose-finding and -expansion phases in patients with B-cell non-Hodgkin lymphoma (B-NHL). The primary end points for part B include AEs, dose-limiting toxicities, and ORR.

The ELM-2 Trial

The ongoing ELM-2 trial is examining odronextamab in adult patients with relapsed/refractory B-NHL, including FL and DLBCL that is relapsed or refractory to at least 2 prior lines of therapy.³ The primary end point is ORR as assessed by independent central review.

Looking to the Past and Building Toward the Future

“[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,” George D. Yancopoulos, MD, PhD, board co-chair, president, and chief scientific officer of Regeneron, added in the news release.¹ “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. We’re also excited to be advancing our broader pipeline of CD3 and other bispecific therapies, both to additional hematologic cancers, such as myeloma, as well as to solid tumors.”

In March 2024, the FDA issued complete response letters to the biologics license applications seeking the FDA approval of odronextamab for the treatment of patients with relapsed/refractory DLBCL or FL who have received 2 or more prior lines of systemic therapy.⁴

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://investor.regeneron.com/news-releases/news-release-details/ordsponotm-odronextamab-approved-european-union-treatment
2. Study to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies (ELM-1). ClinicalTrials.gov. Updated September 7, 2023. Accessed June 28, 2024. https://clinicaltrials.gov/study/NCT02290951
3. A study to assess the anti-tumor activity and safety of odronextamab in adult patients with B-cell non-Hodgkin lymphoma who have been previously treated with other cancer therapies (ELM-2). ClinicalTrials.gov. Updated August 21, 2024. Accessed August 26, 2024. https://clinicaltrials.gov/study/NCT03888105
4. Regeneron provides update on biologics license application for odronextamab. News release. Regeneron Pharmaceuticals, Inc. March 25, 2024. Accessed June 28, 2024. https://investor.regeneron.com/news-releases/news-release-details/regeneron-provides-update-biologics-license-application