Introduction

In ELM-2 (NCT03888105), a Phase 2, open-label, multicohort study, odronextamab monotherapy demonstrated encouraging clinical efficacy, generally manageable safety, and maintenance of patient-reported outcomes in R/R FL (Chong et al. AACR 2024; Tessoulin et al. ASH 2023). In the absence of head-to-head clinical trials comparing CD20×CD3 bispecific antibodies in R/R FL, two unanchored MAICs were conducted to evaluate the efficacy of odronextamab versus mosunetuzumab and epcoritamab in patients with R/R FL in the third-line or later (3L+) setting.

Methods

Patient-level data from the ELM-2 R/R FL cohort receiving odronextamab (N=128; data cutoff: October 2023) were compared with published data from similar cohorts in the GO29781 trial of mosunetuzumab (N=90; Budde et al. Lancet Oncol 2022) and EPCORE NHL-1 trial of epcoritamab (N=128; Linton et al. Lancet Haematol 2024). To adjust for baseline differences in the trial populations, a priori-identified prognostic variables (progression of disease within 2 years, primary refractory, refractory to last line of therapy [LOT], number of prior LOTs, serum lactate dehydrogenase level, Eastern Cooperative Oncology Group performance status, Follicular Lymphoma International Prognostic Index, age at start of LOT, and Ann Arbor disease stage) were included in the base-case MAICs. Two additional variables (double refractory and prior autologous stem cell transplant), reported in ELM-2 and the comparator studies, were included in a sensitivity analysis. The MAICs reported here were focused on response outcomes as assessed by independent central review, which were reported across trials. Relative treatment effects before and after matching were presented as odds ratios (ORs), along with 95% confidence intervals (CIs).

Results

The effective sample size for odronextamab was 102.0 after matching with mosunetuzumab and 90.6 after matching with epcoritamab in the base-case MAICs. All key prognostic variables were balanced between ELM-2 and both comparator trials in each analysis. Before and after matching, odronextamab demonstrated comparable objective response rates (ORRs) and significantly higher complete response (CR) rates versus mosunetuzumab (before matching: ORR 80.5% vs 80.0%, OR 1.03 [95% CI 0.52-2.03], p=0.93; CR rate 73.4% vs 60.0%, OR 1.84 [95% CI 1.04-3.28], p=0.04; after matching: ORR 83.5% vs 80.0%, OR 1.27 [95% CI 0.61-2.65], p=0.53; CR rate 75.7% vs 60.0%, OR 2.08 [95% CI 1.12-3.86], p=0.02). Odronextamab demonstrated numerically higher CR rates versus epcoritamab before and after matching (before matching: CR rate 73.4% vs 62.5%, OR 1.66 [95% CI 0.98-2.82], p=0.06; after matching: CR rate 69.4% vs 62.5%, OR 1.36 [95% CI 0.77-2.41], p=0.29). The ORRs of odronextamab and epcoritamab were comparable before matching (ORR 80.5% vs 82.0%, OR 0.90 [95% CI 0.48-1.69], p=0.75) and after matching (ORR 78.1% vs 82.0%, OR 0.78 [95% CI 0.40-1.53], p=0.47). Consistent results were observed in the sensitivity analyses.

Conclusions

In the absence of head-to-head clinical trials comparing bispecific antibodies in the setting of 3L+ FL, MAICs demonstrate that odronextamab was associated with higher CR rates compared with mosunetuzumab and epcoritamab. Since achieving a CR in the R/R FL setting is an important treatment goal, our results highlight the potential of odronextamab as an effective treatment option in R/R FL.

Disclosures

Jagadeesh:Affimed, Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; AstraZeneca, ATARA Biotherapeutics, Debio Pharma, LOXO Pharmaceuticals, MEI Pharma, Regeneron Pharmaceuticals, Inc., Seagen, Trillium Pharmaceuticals: Research Funding. Novelli:Novartis: Research Funding; Mundipharma: Consultancy. Luminari:BeiGene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Regeneron Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Taszner:Takeda: Consultancy, Speakers Bureau; Roche: Consultancy; Beigene: Consultancy, Speakers Bureau. Merli:Regeneron Pharmaceuticals, Inc.: Consultancy; Johnson and Johnson: Other: Travel expenses; Roche: Other: Travel Expenses. Xu:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Kamat:Regeneron Pharmaceuticals, Inc.: Current Employment. Mastikhina:Precision AQ: Current Employment, Research Funding. Ambati:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Chen:Precision AQ: Current Employment, Research Funding. Chan:Precision AQ: Current Employment, Research Funding. Cope:Precision AQ: Current Employment, Research Funding. Keeping:Precision AQ: Current Employment, Research Funding. Caisip:Precision AQ: Current Employment, Research Funding. Mohamed:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Chaudhry:Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Harnett:Pfizer Inc.: Current holder of stock options in a privately-held company; Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Villasboas Bisneto:Regeneron: Research Funding; Genentech: Research Funding; Epizyme: Research Funding; Enterome: Research Funding; CRISPR: Research Funding; Aptose: Research Funding.

Off Label Disclosure:

Odronextamab, an investigational CD20xCD3 bispecific antibody, for the treatment of patients with relapsed or refractory FL

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2024
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