CHMP Recommends Odronextamab for Relapsed/Refractory FL and DLBCL

The EMA's CHMP has recommended the conditional marketing authorization of odronextamab for relapsed/refractory FL and DLBCL.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for the conditional marketing authorization of odronextamab (REGN1979) in the European Union 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 CHMP recommendation is backed by findings from the phase 1 ELM-1 (NCT02290951) and phase 2 ELM-2 trials (NCT03888105), in which odronextamab elicited durable responses and an acceptable safety profile in these patient populations.

The European Commission is expected to announce a final decision on the conditional marketing authorization in the coming months, according to a news release.

The multicenter, open-label ELM-1 trial is evaluating the safety and tolerability of odronextamab in patients with CD20-positive B-cell malignancies, including FL and DLBCL, who have previously received CD20-directed antibody therapy. This trial includes a cohort of patients who have progressed after CAR T-cell therapy. The primary end points are safety, including the overall frequency of adverse effects (AEs) and dose-limiting toxicities; and overall response rate (ORR).2 Secondary end points include pharmacokinetics, incidence of anti-drug antibodies to odronextamab, incidence of neutralizing antibodies to odronextamab over time, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and duration of complete response (CR).

The open-label, multicenter ELM-2 trial is evaluated odronextamab across 5 disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma, and other B-cell non-Hodgkin lymphoma subtypes.1 The primary end point is ORR per Lugano Classification per independent review committee. Secondary end points include CR, PFS, OS, and DOR.

Updated findings from ELM-2, which were presented at the 2023 ASH Annual Meeting, showed that among 128 evaluable patients with relapsed/refractory FL, the agent generated an 80% ORR and a 73% CR rate.3 At a median follow-up of 18 months (95% CI, 15-28), the median DOR was 23 months (95% CI, 17-not evaluable [NE]), and the median duration of CR was 24 months (95% CI, 18-NE). Furthermore, the median PFS in complete responders was 28 months (95% CI, 20-NE), and the median PFS in all patients was 21 months (95% CI, 17-28). The median OS was not reached (NR; 95% CI, 32 months-NE).

Moreover, findings from the primary phase 2 analysis of ELM-2 in 127 evaluable patients with DLBCL showed a 52% ORR and a 31% CR rate.4 At a median follow-up of 30 months (95% CI, 20-33), the median DOR in all responders was 10 months (95% CI, 5-18), and the median duration of CR was 18 months (95% CI, 10-NE).

Additionally, an analysis from ELM-1 among 44 efficacy-evaluable patients, 73% of whom were refractory to CAR T-cell therapy, showed a 48% ORR and a 30% CR rate. Eight patients converted from a partial response to a CR over the study period. At a median follow-up of 5 months (95% CI, 3-9), the median DOR and median duration of CR were both NR (95% CI, 2 months-NE).

In the pooled safety population between the 2 trials, the most common serious AEs were cytokine release syndrome, pneumonia, COVID-19, and pyrexia.1

Previously, in March 2024, the FDA issued complete response letters to the biologics license applications seeking the approval of odronextamab for patients with relapsed/refractory FL and DLBCL who have received at least 2 prior lines of systemic therapy.5

References

  1. Odronextamab recommended for EU approval by the CHMP to treat relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. News release. Regeneron. June 28, 2024. Accessed June 28, 2024. https://investor.regeneron.com/news-releases/news-release-details/odronextamab-recommended-eu-approval-chmp-treat
  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. Latest odronextamab data in relapsed/refractory follicular lymphoma showed compelling responses and overall maintenance of patient-reported outcomes. News release. Regeneron. December 10, 2023. Accessed June 28, 2024. https://investor.regeneron.com/news-releases/news-release-details/latest-odronextamab-data-relapsedrefractory-follicular-lymphoma
  4. Updated odronextamab data from relapsed/refractory diffuse large B-cell lymphoma pivotal trial showed deep and durable responses and the potential of ctDNA to predict long-term outcomes. News release. Regeneron. December 10, 2023. Accessed June 28, 2024. https://investor.regeneron.com/news-releases/news-release-details/updated-odronextamab-data-relapsedrefractory-diffuse-large-b
  5. Regeneron provides update on biologics license application for odronextamab. News release. Regeneron. March 25, 2024. Accessed June 28, 2024. https://investor.regeneron.com/news-releases/news-release-details/regeneron-provides-update-biologics-license-application