P1083: odronextamab in patients with relapsed/refractory follicular lymphoma grade 1–3a: results from a prespecified analysis of the pivotal phase 2 study elm-2

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Odronextamab is a CD20×CD3 bispecific antibody (Ab). In the Phase 1 ELM-1 study (NCT02290951), odronextamab demonstrated potent antitumor activity and a generally manageable safety profile in patients (pts) with heavily pretreated follicular lymphoma (FL) (Bannerji, et al. Lancet Haematol, 2022). Aims: To conduct a prespecified analysis of the efficacy and safety of odronextamab monotherapy in the FL cohort from the Phase 2 ELM-2 study (NCT03888105). Methods: ELM-2 is a global, multicenter study that enrolled adult pts with FL Grade 1–3a who were relapsed/refractory (R/R) after ≥2 prior lines of therapy (LOT) including an anti-CD20 Ab and an alkylator. Informed consent was obtained from all pts. Intravenous odronextamab was administered in 21-day cycles with steroid prophylaxis and step-up dosing during Cycle (C) 1. The initial step-up regimen consisted of 1 mg split over C1 Day (D) 1 and C1D2, and 20 mg split over C1D8 and C1D9, then the full 80 mg dose on C1D15 (1/20 regimen). This regimen was revised during the study to further mitigate risk of cytokine release syndrome (CRS), with the modified regimen consisting of 0.7 mg split over C1D1 (0.2 mg) and C1D2 (0.5 mg), 4 mg split over C1D8 (2 mg) and C1D9 (2 mg), and 20 mg split over C1D15 (10 mg) and C1D16 (10 mg), then the 80 mg full dose on C2D1 (0.7/4/20 regimen). 80 mg QW continued until the end of C4, followed by 160 mg Q2W until disease progression or unacceptable toxicity. Primary endpoint was ORR assessed by independent central review (ICR). All efficacy data described here are based on ICR. Results: As of Sept 15, 2022, 131 pts had been treated: median age 61 years (range 22–84); male, 53%; FLIPI 3–5, 59%; median prior LOT, 3 (range 2–13); refractory to last therapy, 71%; refractory to anti-CD20 Ab therapy, 75%; progression of disease within 2 years, 48%. Median duration of study follow-up was 22.4 months. ORR and CR rate by ICR were 82% (99/121) and 75% (91/121), respectively. ORR and CR rate were consistent across high-risk subgroups. Responses were durable with both a median duration of response and a median duration of CR of 20.5 months. Median PFS was 20.2 months (95% CI 14.8–not estimable [NE]) and median OS was not reached (95% CI NE–NE). TEAEs occurred in all pts, considered treatment-related in 118 (90%). Treatment-related Grade (Gr) 5 AEs were reported for 3 (2%) pts (pneumonia, progressive multifocal leukoencephalopathy, systemic mycosis [n=1 each]); treatment-related AEs led to discontinuation in 10 (8%) pts. The most common TEAEs (>30% all grades) were CRS (56%), neutropenia (40%), and pyrexia (31%). With the 0.7/4/20 step-up regimen (n=63), Gr 3 CRS was observed in 1 (2%) pt (no Gr 4 or 5 CRS), and all CRS events resolved; 19% of pts received tocilizumab for CRS management. No ICANS was reported with the 0.7/4/20 regimen. COVID-19 was reported by 23 (18%) pts across the study, including Gr ≥3 (n=7 [5%]). Summary/Conclusion: In the ELM-2 study, odronextamab demonstrated compelling efficacy in pts with R/R FL, with 75% of pts achieving CR. Responses were durable, and survival outcomes favorable, in the context of heavily pretreated R/R FL. Odronextamab showed an acceptable safety profile; results with the 0.7/4/20 step-up regimen compared favorably to other CD20×CD3 bispecific antibodies, with only 1 case of Gr ≥3 CRS. In pts with R/R FL, where prognosis is typically poor, odronextamab may provide a more accessible option with favorable benefit/risk compared with existing therapies. Keywords: Follicular lymphoma, Non-Hodgkin’s lymphoma, Bispecific, Relapsed lymphoma