EU’s CHMP Recommends Odronextamab Approval in Follicular Lymphoma, DLBCL

The FDA issued a complete response letter for odronextamab as a treatment for patients with relapsed/refractory DLBCL or follicular lymphoma in March 2024.

The European Medicine Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion in support of granting conditional marketing authorization for odronextamab as a treatment for adult patients with relapsed/refractory follicular lymphoma or diffuse large B-cell lymphoma (DLBCL) following at least 2 prior lines of systemic therapy, according to a press release from the developer, Regeneron Pharmaceuticals, Inc.¹

Data supporting the positive opinion came from the phase 2 ELM-2 trial (NCT03888105) and the phase 1 ELM-1 trial (NCT02290951). Updated findings from both trials were presented at the 2023 American Society of Hematology (ASH) Annual Meeting.

Phase 2 ELM-2 Trial

Among 128 evaluable patients with relapsed/refractory follicular lymphoma in the ELM-2 trial, treatment with odronextamab produced an objective response rate (ORR) of 80% and a complete response (CR) rate of 73%.² Data showed that the median duration of response (DOR) was 23 months (95% CI, 17-not evaluable [NE]) and that the median duration of CR was 24 months (95% CI, 18-NE).

Odronextamab elicited a median progression-free survival (PFS) of 28 months (95% CI, 20-NE) among those with a response and 21 months (95% CI, 17-28) across all patients. Additionally, the median overall survival (OS) was not reached (95% CI, 32-NE).

Investigators reported that the most common adverse effects (AEs) in the follicular lymphoma cohort included cytokine release syndrome (CRS; 56%), neutropenia (48%), pyrexia (36%), anemia (34%), COVID-19 (31%), and infusion-related reactions (31%). Additionally, 1 patient had grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) that did not appear to be related to CRS.

“The odronextamab data presented at ASH in patients with relapsed/refractory follicular lymphoma showcase a strong profile across measures of efficacy, safety and health-related quality of life,” trial investigator Benoît Tessoulin, MD, PhD, from Nantes University Hospital, Nantes; CRCINA, Nantes University, Nantes, France, said in a press release on these findings.²

Of 127 patients in the ELM-2 trial with relapsed/refractory DLBCL, the ORR was 52%, and 31% had a CR.³ Investigators reported responses among subgroups of patients with high-risk features including high-grade double-hit or triple-hit lymphoma and transformed DLBCL. Treatment yielded a median DOR of 10 months (95% CI, 5-18), and the median duration of CR was 18 months (95% CI, 10-NE).

Common AEs in the DLBCL cohort included CRS (55%), pyrexia (43%), anemia (39%), and neutropenia (31%). Investigators highlighted no instances of ICANS.

The ongoing, multicenter ELM-2 trial is evaluating treatment with odronextamab among 375 patients with various subtypes of B-cell non-Hodgkin lymphoma including DLBCL, follicular lymphoma, mantle cell lymphoma (MCL), and marginal zone lymphoma. The trial’s primary end point is ORR based on Lugano classification. Secondary end points include CRs, PFS, overall survival, DOR, disease control rate, safety, and quality of life.

Phase 1 ELM-1 Trial

At the 2023 ASH Annual Meeting, investigators presented findings from the ELM-1 trial on 44 evaluable patients with DLBCL, 73% of whom were refractory to treatment with CAR T-cell therapy. Data showed an ORR of 48% and a CR rate of 30%. Both median DOR and median duration of CR were not reached (95% CI, 2 to NE).

Common AEs in the ELM-1 population included CRS (52%), anemia (34%), pyrexia (34%), and fatigue (34%). All CRS toxicity had resolved with a median time to resolution of 2 days (range, 1-8).

Investigators of the ongoing open-label ELM-1 trial are assessing the safety and tolerability of odronextamab in those with CD20-positive B-cell malignancies previously treated with CD20-directed antibodies. The trial includes an expansion cohort with patients with DLBCL who had progression following prior CAR T-cell therapy.

The FDA issued a complete response letter for odronextamab as a treatment for patients with relapsed/refractory DLBCL or follicular lymphoma in March 2024.⁴ At the time, the agency highlighted issues related to the enrollment status of trials intended to confirm the benefit of odronextamab in the aforementioned patient populations.

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 Pharmaceuticals, Inc. June 28, 2024. Accessed July 1, 2024. https://tinyurl.com/3vjw876z
2. Latest odronextamab data in relapsed/refractory follicular lymphoma showed compelling responses and overall maintenance of patient-reported outcomes. News release. Regeneron Pharmaceuticals, Inc. December 10, 2023. Accessed July 1, 2024. https://tinyurl.com/msmyeu5t
3. 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 Pharmaceuticals, Inc. December 10, 2023. Accessed July 1, 2024. https://tinyurl.com/bdf4dwe9
4. Regeneron provides update on biologics license application for odronextamab. News release. Regeneron Pharmaceuticals, Inc. March 25, 2024. Accessed July 1, 2024. https://tinyurl.com/uwtm4fxb