Regeneron's odronextamab, a CD20xCD3 bispecific antibody, is showing promising results in various B-cell lymphoma subtypes, according to data presented at the ASH Annual Meeting. The trials, OLYMPIA-1, ELM-1, and ELM-2, highlight the drug's potential in both early and late lines of treatment. These findings could significantly impact the treatment landscape for patients with relapsed or refractory lymphomas.
High Response Rates in Follicular Lymphoma
In the safety lead-in portion of the Phase 3 OLYMPIA-1 trial, odronextamab monotherapy led to complete responses (CR) in all 12 evaluable patients with previously untreated follicular lymphoma (FL). This is particularly noteworthy as historical data indicates that the standard-of-care regimen R-Chemo is associated with an objective response rate (ORR) of 89% and a CR rate of 67%. According to Elizabeth Brém, Associate Clinical Professor at UC Irvine, these initial data show the "paradigm-changing potential of odronextamab" in previously untreated patients. The OLYMPIA-1 trial is designed to explore a novel, chemotherapy-free, fixed-duration treatment option for these patients.
Durable Responses in DLBCL After CAR-T Therapy
The ELM-1 trial evaluated patients with diffuse large B-cell lymphoma (DLBCL) who had progressed after CAR-T therapy. The primary analysis from an expansion cohort of this trial showed a 48% objective response rate (ORR), with 32% achieving a complete response (CR). These responses were observed across patients with high-risk features, including those refractory to their last therapy. The median duration of response (DoR) was 15 months (95% CI: 3 months to not estimable [NE]), the median progression-free survival (PFS) was 5 months (95% CI: 3 to 5 months), and the median overall survival (OS) was 10 months (95% CI: 5 to 16 months). For patients achieving CR, medians were not reached in terms of PFS (95% CI: 9 months to NE) and OS (95% CI: 15 months to NE).
Matthew Matasar, M.D., MS, Chief of Blood Disorders at Rutgers Cancer Institute and RWJBarnabas Health, noted the critical unmet need in DLBCL progressing after CAR-T, highlighting that ELM-1 is one of the only trials prospectively evaluating a CD20xCD3 bispecific antibody in this setting.
Significant Efficacy in Marginal Zone Lymphoma
Data from the ELM-2 trial, which focused on heavily pretreated patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL), demonstrated a 77% ORR, with all responders achieving a CR, per investigator assessment. Medians were not reached in terms of DoR (95% CI: 12 months to NE), duration of CR (95% CI: 12 months to NE), PFS (95% CI: 15 months to NE) and OS (95% CI: NE to NE).
Safety Profile
While odronextamab has shown promising efficacy, adverse events were also reported. In the OLYMPIA-1 trial, Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 46% of patients. In the ELM-1 trial, all patients experienced TEAEs, with 77% experiencing Grade ≥3 TEAEs. The ELM-2 trial reported Grade ≥3 TEAEs in 83% of patients. Cytokine release syndrome (CRS) was a common adverse event across all trials, with most cases being Grade 1 or 2.
Regulatory Status and Future Plans
Odronextamab is currently approved in the European Union as Ordspono™ for certain lymphoma indications. Regeneron plans to resubmit the drug for U.S. regulatory approval in the first half of 2025 for relapsed/refractory follicular lymphoma after two or more lines of systemic therapy. The potential use of odronextamab in R/R MZL is investigational and has not been approved by any regulatory authority.
Regeneron's extensive clinical program, including the OLYMPIA and ELM trials, continues to explore the potential of odronextamab in various B-NHL subtypes and treatment lines. These trials are crucial in determining the long-term efficacy and safety of odronextamab and its role in the evolving landscape of lymphoma treatment.
