The results are promising for patients with relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma, and the trial is ongoing to assess the efficacy of odronextamab in other subtypes.
Trial Name: A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Patients With B-cell Non-Hodgkin Lymphoma That Have Been Previously Treated (ELM-2)
ClinicalTrials.gov ID: NCT03888105
Sponsor: Regeneron Pharmaceuticals
Completion Date (Estimated): February 5, 2028
Odronextamab (REGN1979; Regeneron Pharmaceuticals) is a novel CD20xCD3 bispecific antibody with a generally manageable safety profile that has previously demonstrated consistent anti-lymphoma activity in patients with relapsed or refractory (R/R) follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL). In the prior phase 1 trial ELM-1, investigators observed promising results in patients treated with odronextamab who relapsed following chimeric antigen receptor (CAR) T-cell therapy.1
In this current open-label phase 2 clinical trial ELM-2 (NCT03888105), patients with different types of B-cell non-Hodgkin lymphoma (B-NHL) were treated with odronextamab. Depending on their disease state, patients were assigned to different cohorts: FL (grades 1-3a), DLBCL, R/R mantle cell lymphoma (this cohort also included patients who relapsed or have disease that is refractory to prior systemic therapy, or patients with an intolerance to Bruton tyrosine kinase inhibitor therapy who have progressed after other systemic therapy), marginal zone lymphoma, and patients with other B-NHL subtypes. Regardless of their B-NHL subtype, all patients received IV infusions of odronextamab.2
Currently, data on the FL and DLBCL cohorts are available.1,3 Odronextamab was administered weekly in 21-day cycles during cycles 1 through 4. Additionally, the treatment was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg during cycle 1 to mitigate the risk of cytokine release syndrome (CRS), followed by 160 mg on days 1, 8, and 15 of cycles 2 through 4. Additionally, after cycle 4, maintenance treatment with 3320 mg of odronextamab continued every 2 weeks until disease progression or unacceptable toxicity. Patients who achieved a complete response (CR) that was durable for 9 months or longer were able to transition dosing to every 4 weeks. Further, final analyses were performed when all patients had the opportunity for a follow-up at 36 weeks or later.1,3
The primary end point for the trial is objective response rate (ORR), which was assessed from first dose until all patients completed the treatment duration or withdrawal (FL cohort: 52 weeks; DLBCL cohort: 36 weeks). Key secondary end points include CR rate, duration of response (DoR), progression-free survival (PFS), overall survival (OS), and changes in scores of patient-reported outcomes.1-3
In the DLBCL cohort, a total of 127 patients with a median age of 66 years (range: 24-88) were evaluable for efficacy and had a median duration of follow-up of 26.2 months. The median of prior lines of therapy was 2 (range: 2-8) with approximately 57% were primary refractory and 66% were double refractory to an anti-CD20 antibody and an alkylator in any line of therapy. Additionally, patient-reported outcomes were either maintained or improved, and both patient-reported pain and emotional functioning scores were observed to improve from baseline during the treatment duration.1
The results indicated that ORR and CR rate were 52% (n = 66) and 31% (n = 39), respectively, and were consistent across high-risk subgroups. Additionally, the median DoR was 10.2 months (95% CI: 5.0-not estimable [NE]) and median duration of CR was 17.9 months (95% CI: 9.2-NE), with an approximate 48% probability of maintaining CR for 24 months.1
According to the investigators, safety was generally consistent with previous reports. Treatment-related adverse events (AEs) that led to interruption or delay of odronextamab treatment occurred in 75 patients (53%) and discontinuation in 14 patients (10%). The most common treatment-emergent AEs reported by the DLBCL cohort were CRS (55%), anemia (43%), and pyrexia (42%), and in the step-up regimen (n = 74), approximately 98% of CRS events were grade 1 or 2, with only 1 grade 3 occurrence (which was confounded by pancreatitis). CRS events resolved with supportive measures, with 26% of patients receiving tociliazumab for management with the optimized regimen. Further, grade 3 or higher infections were reported by 52 patients (37%), of which 16 (11%) were grade 5. COVID-19 infection was also reported by 23 patients (16%), of which 6 (4%) had grade 5 occurrences.1
A total of 128 patients with a median age of 61 years (range, 22-84) in the FL grade 1 through 3a cohort were evaluable for efficacy of safety at a median follow-up of 20.1 months. The median of prior lines of therapy was 3 (range: 2-13) with 74.2% refractory to an anti-CD20 antibody, and 71.9% refractory to last treatment. Additionally, the median number of treatment cycles was 19.4 (range: 0.1-95.9), with approximately 95.3% and 85.2% of patients completing cycles 1 and 4, respectively. The ORR was approximately 80.5% and CR rate was 73.4%, and the median PFS was 20.7 months with the 24-month PFS being 46.1%. According to the investigators, median OS was not reached, but the 24-month OS was 70.1%.3
Treatment-emergent AEs were present in all patients, with 15.6% having AEs that lead to treatment discontinuation. In the step-up regimen group (n = 60), CRS occurrences were mostly low-grade—with 1 patient experiencing a grade 3 event—and occurred during the first cycle and resolved in a median of 2 days. Additionally, rates of infection were consistent with heavily pretreated, immunocompromised patients and occurred in 102 patients (79.7%). Of these patients, approximately 14.0% experienced grades 4 or 5 infections and 36.7% reported COVID-19 infections.3
The trial is still undergoing to assess the efficacy of odronextamab in other B-NHL subtypes. Additionally, the findings support the continued investigation of this bispecific antibody in phase 3 trials.1-3
References
