Odronextamab receives EC approval for adult patients with R/R FL and DLBCL

On August 26, 2024, it was announced that the European Commission (EC) has approved odronextamab, a CD20xCD3 bispecific antibody, for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), who progress after ≥2 lines of systemic therapy, including a chimeric antigen receptor (CAR) T-cell therapy. This announcement is based on key results from the ELM-1 (NCT02290951) and ELM-2 (NCT03888105) clinical trials, where odronextamab demonstrated robust, durable response rates and an acceptable safety profile in adults with R/R FL or R/R DLBCL. Odronextamab previously received a positive CHMP opinion from the European Medicines Agency for the treatment of patients with R/R FL and R/R DLBCL.

ELM-1  and ELM-2 trials¹

ELM-1 is an ongoing multicenter, open-label, phase I trial investigating the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies who have undergone prior treatment with CD20-directed antibody therapy, including a cohort of patients who have progressed following CAR T-cell therapy.

• In 60 patients with R/R DLBCL, the objective response rate (ORR) in those who had progressed after CAR T-cell therapy was 48%, with 32% achieving a complete response (CR).

• Among responders (n = 29), the median duration of response (DoR) was 15 months.

ELM-2 is an ongoing, open-label, multicenter, pivotal phase II trial investigating the efficacy of odronextamab in adult patients with B-cell non-Hodgkin's lymphoma (B-NHL). The primary endpoint is ORR according to the Lugano Classification, as assessed by an independent review committee (IRC), and secondary endpoints include CR, progression-free survival, overall survival, and DoR.

• In 128 patients with R/R FL, ORR was 80%, with 73% achieving a CR.
• In those achieving CR, the median DoR was 25 months.
• In 127 patients with R/R DLBCL, ORR in CAR T-cell therapy naïve patients was 52%, with 31% achieving a CR.
• In those achieving CR, the median DoR was 18 months.

The most common adverse reactions were cytokine release syndrome (54%), neutropenia (41%), pyrexia (39%), anemia (38%), thrombocytopenia (27%), diarrhea (24%), and COVID-19 (22%).