Final Analysis of the Phase 2 ELM-2 Study: Odronextamab in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

Background Odronextamab is a novel, off-the-shelf, CD20×CD3 bispecific antibody that has demonstrated consistent anti-lymphoma activity and a generally manageable safety profile in heavily pretreated patients (pts) with both R/R follicular lymphoma and R/R DLBCL. Encouraging results have been reported in pts who have relapsed following chimeric antigen receptor (CAR) T-cell therapy in the Phase 1 ELM-1 study, and in pts with R/R DLBCL in the Phase 2 ELM-2 study (Kim WS, et al. ASH. 2022). Here, we present the final analysis of the R/R DLBCL cohort from ELM-2 (NCT03888105), reporting long-term efficacy and safety outcomes. Methods Intravenous odronextamab was administered weekly in 21-day cycles during Cycles (C) 1-4. Optimization of the step-up regimen to further mitigate cytokine release syndrome (CRS) was reported previously (Kim WS, et al. ASH 2022). Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg during C1, followed by 160 mg on Days 1, 8, and 15 of C2-4. After C4, odronextamab maintenance treatment continued at 320 mg every 2 weeks until disease progression or unacceptable toxicity. Pts who achieved a complete response (CR) that was durable for ≥9 months transitioned to dosing every 4 weeks. The final analysis was performed when all pts had the opportunity for ≥36 weeks of follow-up. The primary endpoint was objective response rate (ORR), assessed by independent central review (ICR) according to the Lugano classification. Key secondary endpoints included CR rate, duration of response (DoR), progression-free survival (PFS), overall survival (OS), and changes in scores of patient-reported outcomes. Minimal residual disease (MRD) was included as an exploratory endpoint. Results At the time of data cut-off (Jan 31, 2023) the DLBCL cohort was fully enrolled; 141 pts were evaluable for safety and 127 were evaluable for efficacy, with a median duration of follow-up of 26.2 months. In the safety-evaluable DLBCL population, median age was 66 years (range 24-88), 60% male, 80% Ann Arbor stage III-IV, 56% IPI score ≥3, and median prior lines of therapy was 2 (range 2-8). 17% of pts had transformed disease from indolent lymphoma and 5% had Richter's transformation; 12% were double-hit and 6% triple-hit. In total, 57% of pts were primary refractory and 66% were double refractory to an anti-CD20 antibody and an alkylator in any line of therapy. ORR and CR rate confirmed by ICR were 52% (66/127) and 31% (39/127), respectively,