Regeneron announces new data from odronextamab trial at ASH

Regeneron (REGN) announced new and updated data for odronextamab were presented at the 66th American Society of Hematology, or ASH, annual meeting and exposition in San Diego. The presentations, including two orals, showcase the depth and breadth of the odronextamab clinical development program, with twelve abstracts spanning several B-cell non-Hodgkin lymphoma subtypes across earlier lines of treatment. The ongoing Phase 3 OLYMPIA-1 confirmatory trial consists of a non-randomized safety run-in followed by a randomized efficacy portion evaluating odronextamab monotherapy versus rituximab plus standard-of-care chemotherapies. In Part 1, odronextamab led to complete responses in all 12 patients evaluable for efficacy at week 12. Historical clinical trial data indicate that the standard-of-care regimen R-Chemo was associated with an objective response rate of 89% and 67% CR rate. Among the 13 patients evaluable for safety, none experienced a dose-limiting toxicity. The most common treatment-emergent adverse events were cytokine release syndrome, diarrhea and rash. All cases of CRS were Grade 1. Infections occurred in 39% of patients, and 15% experienced a Grade 3 infection. Grade 3 TEAEs occurred in 46% of patients, which included one patient who discontinued early due to elevated liver enzymes. There were no reports of tumor lysis syndrome, or TLS, or immune effector cell associated neurotoxicity syndrome, or ICANS. The primary analysis from an expansion cohort of the ELM-1 trial, which evaluated patients with DLBCL who progressed after CAR-T therapy, were presented in an oral session. Among 60 patients – with a median duration of treatment of 12 weeks and a median duration of follow-up of 16 months – results assessed by independent central review showed: 48% ORR, with 32% achieving a CR. These responses were observed across patients with high-risk features, including those that were refractory to their last therapy, double refractory, or refractory prior to CAR-T. Among all patients, there was a 15-month median duration of response, 5-month median progression-free survival and a 10-month median overall survival. Among CR patients, medians were not reached in terms of PFS and OS. All patients experienced TEAEs, including 77% who experienced Grade 3 TEAEs. CRS occurred in 48% of patients. Infections occurred in 50% of patients, and 20% experienced a Grade 3 infection, including one treatment-related death due to COVID-19 pneumonia. No TLS or ICANS cases were reported. Another oral presentation featured data from a cohort of heavily pretreated patients with relapsed/refractory MZL, a setting with no approved treatment options. In the potentially pivotal ELM-2 trial, 42 patients were enrolled, of which 35 patients were evaluable for efficacy. At a median duration of follow-up of 11 months, results showed: 77% ORR, with all responders achieving a CR, per investigator assessment. Medians were not reached in terms of DoR, duration of CR, PFS and OS. Among 42 patients evaluated for safety, the most common TEAEs were CRS, infusion-related reaction, pyrexia and neutropenia. Grade 3 TEAEs occurred in 83% of patients and included neutropenia and increased levels of alanine aminotransferase and aspartate aminotransferase. Infections occurred in 69% of patients, and 24% experienced a Grade 3 infection. Four patients discontinued treatment due to TEAEs. Odronextamab is approved in the European Union as Ordspono to treat R/R FL or DLBCL after two or more lines of systemic therapy but its safety and efficacy have not been fully evaluated by any other regulatory authority. For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu. The U.S. regulatory resubmission for odronextamab in R/R FL after two or more lines of systemic therapy is expected to be submitted in the first half of 2025. The potential use of odronextamab in R/R MZL is investigational and has not been approved by any regulatory authority.