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Clinical Trial
. 2025 Mar;6(3):528-539.
doi: 10.1038/s43018-025-00921-6. Epub 2025 Mar 17.

Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial

Won Seog Kim  1 , Tae Min Kim  2 , Seok-Goo Cho  3 , Isidro Jarque  4 , Elżbieta Iskierka-Jażdżewska  5 , Li Mei Poon  6 , H Miles Prince  7 , Huilai Zhang  8 , Junning Cao  9 , Mingzhi Zhang  10 , Benoît Tessoulin  11 , Sung Yong Oh  12 , Francesca Lim  13 , Cecilia Carpio  14 , Tran-Der Tan  15 , Sabarish Ayyappan  16 , Antonio Gutierrez  17 , Jingxian Cai  18 , Melanie Ufkin  18 , Saleem Shariff  19 , Jurriaan Brouwer-Visser  18 , Aafia Chaudhry  18 , Hesham Mohamed  18 , Srikanth Ambati  18 , Jan Walewski  20 ; ELM-2 Investigators
Collaborators, Affiliations
Clinical Trial

Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial

Won Seog Kim et al. Nat Cancer. 2025 Mar.

Erratum in

Abstract

The phase 2, multicohort, ongoing ELM-2 study evaluates odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma after ≥2 lines of therapy. Here primary analysis of the diffuse large B cell lymphoma (DLBCL) cohort is reported. Patients received intravenous odronextamab in 21-day cycles until progression or unacceptable toxicity, with cycle 1 step-up dosing to mitigate cytokine release syndrome (CRS) risk. The primary endpoint was objective response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response, progression-free survival (PFS) and overall survival. A total of 127 patients were enrolled. At the 29.9-month efficacy follow-up, the ORR was 52.0% and CR rate was 31.5%. Median durations of response and CR were 10.2 and 17.9 months, respectively. Undetectable minimal residual disease at cycle 4 day 15 was associated with PFS benefit. With a step-up of 0.7 to 4 to 20 mg (n = 60), CRS was the most common treatment-emergent adverse event (53.3% (grade ≥3, 1.7%)). No immune effector cell-associated neurotoxicity syndrome was reported. Infections were reported in 82/127 (64.6%) patients (grade ≥3, 38.6%; coronavirus disease 2019, 18.1% (grade ≥3, 12.6%)). In conclusion, odronextamab showed encouraging efficacy in heavily pretreated R/R DLBCL and generally manageable safety with supportive care. Clinical trial registration: NCT03888105 .

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Conflict of interest statement

Competing interests: W.S.K. reports research funding from BeiGene, Boryung, Donga, Kyowa-Kirin, Roche and Sanofi. T.M.K. reports honoraria from Amgen, AstraZeneca, IMBDx, Janssen, MedImmune and Takeda, trial research funding to institution from AstraZeneca, consultancy for AstraZeneca, Boryung, F.Hoffmann-La Roche, Janssen, MedImmune, Novartis, Regeneron Pharmaceuticals, Inc., Roche, Samsung Bioepis, Takeda and Yuhan, speaker bureau fees for IMBDx, Janssen and Takeda, membership on an entity’s board of directors or advisory committees for BeiGene, Janssen, Novartis, Regeneron Pharmaceuticals, Inc., Roche and Takeda and an uncompensated relationship with AstraZeneca, Boryung, MedImmune, Novartis and Roche. I.J. reports consultancy for Amgen, AstraZeneca, Kyowa-Kirin, Novartis, Pfizer, Sobi and Takeda, research funding from Amgen, AstraZeneca, BeiGene, Incyte, Janssen, Regeneron Pharmaceuticals, Inc., Sobi and Takeda and honoraria fees from AstraZeneca, Incyte, Janssen, Novartis, Pfizer, Sobi and Takeda. E.I.-J. reports consultancy for AbbVie and AstraZeneca and honoraria from AbbVie, AstraZeneca, Janssen and Novartis. L.M.P. reports research funding from Regeneron Pharmaceuticals, Inc. B.T. reports honoraria from AbbVie, Gilead, Incyte and Kite. C.C. reports honoraria from Gilead, Novartis, Regeneron Pharmaceuticals, Inc. and Takeda, consultancy for BMS, Regeneron Pharmaceuticals, Inc. and Takeda and membership on an entity’s board of directors or advisory committees for Regeneron Pharmaceuticals, Inc. and Takeda. Sa.A. reports membership on an entity’s board of directors or advisory committee for AbbVie, AstraZeneca, BeiGene, Fate Therapeutics and Regeneron Pharmaceuticals, Inc., consultancy for ADC Therapeutics and AstraZeneca and speaker bureau fees from BeiGene and Genentech. J. Cai, M.U., S.S., J.B.-V., A.C., H.M. and S. Ambati hold stock or stock options for and are employees of Regeneron Pharmaceuticals, Inc. J.W. reports consultancy for AbbVie, Gilead, Novartis, Roche, Takeda and MSD, research or clinical trial funding from GSK, Novartis and Roche and honoraria from AbbVie, Amgen, Gilead, GSK, Novartis, Roche and Takeda. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Waterfall plot of best percentage change from baseline in tumor sum of the products of the diameters.
Data for each evaluable patient are shown as a separate bar on the figure (n = 90 patients). SD, stable disease. Source data
Fig. 2
Fig. 2. Subgroup analysis of ORR by ICR.
ORR data are presented as the mean values ± 95% CIs. The vertical dashed line indicates the ORR for all patients (N = 127). Source data
Fig. 3
Fig. 3. PFS and OS in patients treated with odronextamab, for all patients and by best overall response.
a, PFS. b, OS. Data are presented as Kaplan–Meier curves, with tick marks indicating patients with censored data (N = 127 patients; n = 40 with CR, n = 26 with PR). Median values with 95% CIs are presented alongside the respective curves. Source data
Fig. 4
Fig. 4. PFS by C4D15 ctDNA MRD status.
Data are presented as Kaplan–Meier curves, with tick marks indicating patients with censored data (n = 63 ctDNA-evaluable patients; n = 20 with cleared MRD at C4D15, n = 43 with detected MRD at C4D15). Median values with 95% CIs are presented alongside the respective curves. The HR for PFS in patients with MRD cleared versus MRD detected was calculated by univariate Cox regression. Source data
Extended Data Fig. 1
Extended Data Fig. 1. Patient disposition for the DLBCL cohort.
N = 127 patients enrolled into the DLBCL cohort and evaluated for efficacy and safety. n numbers represent the number of patients who received the 1/20 mg or 0.7/4/20 mg cycle 1 step-up dosing regimens, those who discontinued treatment (and reasoning), and those with ongoing treatment at the time of data cut-off (August 18, 2023). DLBCL, diffuse large B-cell lymphoma. Source data
Extended Data Fig. 2
Extended Data Fig. 2. PFS by C4D15 ctDNA MRD status in patients with DLBCL and no CR at C4D15.
N = 35 ctDNA-evaluable patients (n = 8 with cleared MRD at C4D15; n = 27 with detected MRD at C4D15). Data are presented as Kaplan–Meier curves, with tick marks indicating patients with censored data. The HR for PFS in patients with MRD cleared versus MRD detected was calculated by univariate Cox regression. C4D15, cycle 4 day 15; CI, confidence interval; CR, complete response; ctDNA, circulating tumor DNA; DLBCL, diffuse large B-cell lymphoma; HR, hazard ratio; MRD, minimal residual disease; PFS, progression-free survival. Source data
Extended Data Fig. 3
Extended Data Fig. 3. Treatment-emergent CRS by dose and severity grade with the 0.7/4/20 mg regimen.
The percentage of patients in the 0.7/4/20 mg regimen cohort who experienced at least one CRS event are shown according to CRS grade (1, 2, or 3). n numbers represent the number of patients treated at each of the dose points shown. CRS, cytokine release syndrome. Source data
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