Regeneron Pharmaceuticals presented new data at the 66th American Society of Hematology (ASH) Annual Meeting, highlighting the potential of odronextamab in treating various B-cell non-Hodgkin lymphomas (B-NHL). The data span multiple subtypes and lines of treatment, showcasing the drug's versatility and efficacy.
OLYMPIA-1 Trial: High Complete Response Rate in Follicular Lymphoma
The Phase 3 OLYMPIA-1 trial, which includes a safety run-in (Part 1) followed by a randomized efficacy portion (Part 2), is evaluating odronextamab monotherapy against rituximab plus standard-of-care chemotherapies in follicular lymphoma (FL). In Part 1 (N=13), odronextamab led to complete responses (CR) in all 12 patients evaluable for efficacy at week 12.
Elizabeth Brém, Associate Clinical Professor at UC Irvine, noted, "These compelling, initial data show the paradigm-changing potential of odronextamab in previously untreated patients and reinforce the remarkable complete response rates odronextamab demonstrated in late-line follicular lymphoma."
Among the 13 patients evaluable for safety, none experienced a dose-limiting toxicity (DLT). The most common treatment-emergent adverse events (TEAEs) were cytokine release syndrome (CRS; 62%), diarrhea (46%), and rash (39%). 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 (TLS) or immune effector cell associated neurotoxicity syndrome (ICANS).
ELM-1 Trial: Durable Responses in DLBCL After CAR-T Therapy
The primary analysis from an expansion cohort of the ELM-1 trial, which evaluated patients with diffuse large B-cell lymphoma (DLBCL) who progressed after CAR-T therapy, was presented. Among 60 patients – with a median duration of treatment of 12 weeks (range <1 to 154 weeks) and a median duration of follow-up of 16 months – results assessed by independent central review showed:
- 48% objective response rate (ORR), with 32% achieving a complete response (CR).
- A 15-month median duration of response (DoR) (95% confidence interval [CI]: 3 months to not estimable [NE]), 5-month median progression-free survival (PFS) (95% CI: 3 to 5 months), and a 10-month median overall survival (OS) (95% CI: 5 to 16 months).
Matthew Matasar, M.D., MS, Chief of Blood Disorders at Rutgers Cancer Institute, stated, "It is encouraging to see these outcomes with odronextamab in a patient population that to date has had an incredibly poor prognosis and limited treatment options."
All patients experienced TEAEs, including 77% who experienced Grade ≥3 TEAEs. CRS occurred in 48% of patients (25% were Grade 1 and 23% were Grade 2). 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.
ELM-2 Trial: High Efficacy in Marginal Zone Lymphoma
Data from a cohort of heavily pretreated patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL), a setting with no approved treatment options, were featured. 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 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).
Among 42 patients evaluated for safety, the most common TEAEs (≥15%) were CRS (55%; all were Grade 1 or 2), infusion-related reaction (36%), pyrexia (36%), and neutropenia (31%). 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 (10%) discontinued treatment due to TEAEs.
Regulatory Outlook
Odronextamab is approved in the European Union as Ordspono™ for R/R FL or DLBCL after two or more lines of systemic therapy. The U.S. regulatory resubmission for odronextamab in R/R FL after two or more lines of systemic therapy is expected 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.
