FDA Denies Approval of Odronextamab in DLBCL and Follicular Lymphoma

• The FDA has issued 2 complete response letters for the biologics license application (BLA) of odronextamab (REGN1979).
• These indications are for patients with relapsed/refractory follicular lymphoma and relapsed/refractory diffuse large B-cell lymphoma (DLBCL), both after 2 or more lines of systemic therapy.
• The potential use of odronextamab in DLBCL and follicular lymphoma is currently under clinical development; however, the agent has not yet been approved by any regulatory authority.

Two complete response letters have been issued by the FDA for the BLA for odronextamab in relapsed/refractory follicular lymphoma and in relapsed/refractory DLBCL after 2 or more lines of systemic therapy.¹

The complete response letters are related to the enrollment status of confirmatory trials that are evaluating the agent. There were no issues regarding the efficacy or safety of odronextamab, as well as no issues regarding trial design, labeling, or manufacturing.

“Odronextamab is a CD3xCD20 antibody that directs T-cell function against B-cell malignancies. It showed significant clinical efficacy in a phase 1 trial. ELM-2 [NCT03888105] is a phase 2 trial looking at both diffuse large B-cell lymphoma and follicular lymphoma,” Jon E. Arnason, MD, physician scientist at Beth Israel Deaconess Medical Center, Boston, Massachusetts, told Targeted Oncology^TM, in an interview.

Lymphomas: © David A Litman - stock.adobe.com

About Odronextamab

The FDA granted priority review to the BLA seeking the approval of odronextamab in September 2023, supported by findings from the phase 1 ELM-1 (NCT02290951) and phase 2 ELM-2 trials.

At the 2023 American Society of Hematology Annual Meeting, data from the final analysis of the ELM-2 trial were reported, demonstrating that at a median follow-up for efficacy of 29.9 months (range, 20.4-32.6), the objective response rate (ORR) among the 127 patients with relapsed/refractory DLBCL who were naive to chimeric antigen receptor (CAR) T-cell therapy was 52%. The complete response (CR) rate was 31.5%, and the median duration of response (DOR) was 10.2 months (95% CI, 5.0-17.9).²

In his presentation, Sabarish Ram Ayyappan, MD, medical director of hematologic malignancies, City of Hope Cancer Treatment Center, Atlanta, noted that response data for odronextamab were consistent with results from the phase 1 ELM-1 trial (NCT02290951) of the safety and efficacy of odronextamab in patients with relapsed or refractory non-Hodgkin lymphoma.³

“The responses were durable with a median duration of complete response up to 18 months. At 24 months, the CR rate was maintained in 47% of the patients. The safety of the drug also was evaluated and consistent with previous reports that odronextamab is safe in patients who received them with relapsed/refractory diffuse large B-cell lymphoma,” explained Ayyappan in an interview with Targeted Oncology^TM.

In the ELM-1 trial, odronextamab was evaluated in patients who previously received CAR T-cell therapy. Among those treated with odronextamab, the ORR was 33.3% and the CR rate was 26.7%. The median DOR was not reached.

In addition to these trials, randomized phase 3 trials of odronextamab in earlier lines of therapy are underway.¹ This includes the OLYMPIA-3 trial (NCT06091865) which is evaluating the agent in patients with previously untreated DLBCL, and the OLYMPIA-4 trial in patients with relapsed/refractory disease. The FDA has required that both of these trials include dose-finding and confirmatory portions.

REFERENCES:

1. Regeneron provides update on biologics license application for odronextamab. News release. Regeneron. March 25, 2024. Accessed March 25, 2024. https://tinyurl.com/38dhaxh6

2. Ayyappan S, Kim WS, Kim TM, et al. Final Analysis of the Phase 2 ELM-2 Study: Odronextamab in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). Blood. 2023;142(1):436. doi:10.1182/blood-2023-179818.

3. Kim TM, Taszner M, Cho SG, et al. Odronextamab in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Grade 1-3a: Results from a Prespecified Analysis of the Pivotal Phase II Study ELM-2. Blood. 2022;140(1):2280–2282. doi:10.1182/blood-2022-158404.