Odronextamab Demonstrates Durability and Safety for Relapsed/Refractory DLBCL

ELM-2 Trial Update

Odronextamab therapy demonstrated durable responses with a tolerable toxicity profile among patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who had received at least 2 prior lines of therapy, according to findings from a phase 2 clinical trial published in Nature Cancer.

This ongoing multicohort study was the second phase to the ELM-2 trial, which evaluated odronextamab, a CD20-CD3 bispecific antibody, administered intravenously in 21-day cycles until disease progression or unacceptable toxicity. A step-up dosing strategy in cycle 1 (0.7 to 4 to 20 mg) was used to mitigate cytokine release syndrome (CRS).

The primary end point was objective response rate (ORR). Secondary end points included complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Overall, 127 patients were included with 60 patients receiving step-up dosing. At 29.9 months, for all patients the ORR was 52.0% and the CR rate was 31.5%. Median DOR was 10.2 months, and the median CR duration was 17.9 months. An improvement with PFS was associated with undetectable minimal residual disease (MRD) at cycle 4, day 15.

Among patients who received step-up dosing, CRS occurred in 53.3% of patients, with grade ≥ 3 CRS reported in 1.7% of patients. Over half of patients reported infections (64.6%) with 38.6% grade ≥3. COVID-19 accounted for 18.1% of infections among patients with 12.6% grade ≥3.

“In conclusion, odronextamab showed encouraging efficacy in heavily pretreated R/R DLBCL and generally manageable safety with supportive care,” the researchers concluded.

Source:

Kim WS, Kim TM, Cho SG, et al. Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial. Nature Cancer. Published online March 17, 2025. doi: 10.1038/s43018-025-00921-6