Ordspono (odronextamab) / Regeneron, ZAI Lab - LARVOL DELTA

Follicular Lymphoma: Current Therapeutic Landscape and Future Prospects (ICML 2025) - P3 | "Abbreviations: 1L = first line; AZD0486 = CD19 × CD3 BsAb; B = bendamustine; CHOP = cyclophosphamide, doxorubicin, vincristine, prednisolone; CIT = chemo-immunotherapy; CR = complete response; CR30 = complete response at 30 months; CVP = cyclophosphamide, vincristine, prednisolone; FLIPI = follicular lymphoma international prognostic index; O = obinutuzumab; PFS = progression free survival; PR = partial response; R = rituximab; R2 = rituximab and lenalidomide...Since 2021, three CAR-T constructs—axicabtagene-ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel)—and three CD3 × CD20 BsAbs—mosunetuzumab, epcoritamab, and odronextamab—have gained regulatory approval in Europe and/or US as options for third line and later...Loncastuximab tesirine (CD19-directed ADC) shows promising activity in 2L+ R/R FL (CR 67%, manageable toxicity in a small Phase 2 cohort) [40]. Adding tafasitamab, an anti-CD19 antibody, to R2 in R/R FL..."

IO biomarker • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • EZH2 • IGH

Odronextamab for Relapsed and Refractory Large B-cell Lymphomas Before CAR-T (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: University of Washington | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma

Comparative analysis of adverse event profiles for CAR-T cell therapies and bispecific antibodies in lymphoma. (ASCO 2025) - " A retrospective analysis was conducted using the FAERS database to assess AE reports associated with CAR-T therapies (Breyanzi, Kymriah, Yescarta, and Tecartus) and BsAbs (Epcoritamab, Glofitamab, Odronextamab, Mosunetuzumab, and Plamotamab). This analysis highlights key differences in the safety profiles of CAR-T and BsAb therapies for lymphoma. CAR-T therapies were associated with a higher incidence of neurological and psychiatric AEs, while BsAbs demonstrated a greater risk of infections. These findings may offer valuable guidance for clinicians in therapy selection and underscore the importance of vigilant monitoring, particularly for neurological toxicities in CAR-T treatments and infection-related risks with BsAbs."

Adverse events • CAR T-Cell Therapy • CNS Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mental Retardation • Musculoskeletal Diseases • Oncology • Psychiatry

BIOMARKER ANALYSES OF THE INFLAMMATORY PROFILE AND MRD CLEARANCE IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) MARGINAL ZONE LYMPHOMA (MZL) VERSUS FOLLICULAR LYMPHOMA (FL) TREATED WITH ODRONEXTAMAB (EHA 2025) - P2 | "This biomarker analysis demonstrated T-cell activation, B-cell depletion, and substantial ctDNA reduction with odronextamab Tx, with a more pronounced inflammatory profile in R/R MZL vs FL (higher cytokine peaks, BL B-cell counts, and naïve T-cell proportions). Additional data from the ongoing ELM-2 study will be presented."

Biomarker • Clinical • IO biomarker • B Cell Non-Hodgkin Lymphoma • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD4 • CD8 • IFNG • IL6 • PD-1

BASELINE INFLAMMATION PREDICTS RESPONSE TO CD3XCD20 BISPECIFIC T CELL ENGAGERS IN RELAPSED/REFRACTORY LARGE B CELL LYMPHOMA (EHA 2025) - "In this retrospective, multicenter study, we analyzed 166 r/r LBCL patients treated with glofitamab (n=137), epcoritamab (n=27) or odronextamab (n=2) monotherapy across 14 centers worldwide. In this international, multicenter cohort, the HEMATOTOX and InflaMix models emerged as robust predictors of adverse outcomes in r/r LBCL patients treated with CD3xCD20 bsAb. These findings support the prospective evaluation of inflammation-based scoring systems to identify patients who are at high risk of treatment failure and hence might benefit from novel combinatorial strategies within clinical trials."

IO biomarker • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

LONGITUDINAL TARGETED CTDNA ANALYSIS TO ASSESS CD20 AND BAFF MUTATIONS IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) FL OR DLBCL PROGRESSING ON ODRONEXTAMAB TREATMENT IN THE ELM-2 STUDY (EHA 2025) - P2 | "This analysis suggests that disease progression in pts with R/R FL or DLBCL treated with odronextamab could be partially attributable to Tx-emergent CD20 and BAFF mutations and shows the utility of minimally invasive ctDNA analysis beyond MRD determination. More mutations were detected with CAPP-Seq vs WGS, possibly due to greater sequencing depth. Ongoing analyses of ctDNA samples at earlier timepoints will help determine whether CD20/BAFF variant detection before PD helps predict clinical outcomes."

Circulating tumor DNA • Clinical • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD22 • CD58 • CD79B

COMPARATIVE EFFECTIVENESS OF ODRONEXTAMAB VERSUS REAL-WORLD SYSTEMIC THERAPIES USED IN AN EXTERNAL CONTROL ARM IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (EHA 2025) - P=N/A, P2 | "Odronextamab was associated with clinically meaningful and higher ORR and CR rates vs 3L+ systemic therapies used in real-world settings. Odronextamab also demonstrated favorable PFS and longer OS and TTNTd. These results support the potential of odronextamab as an off-the-shelf, novel, and effective treatment option that can improve outcomes in 3L+ R/R FL."

Clinical • HEOR • Real-world • Real-world evidence • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

LONG-TERM EFFICACY AND SURVIVAL OUTCOMES WITH ODRONEXTAMAB FOR PATIENTS (PTS) WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (R/R FL): 2-YEAR FOLLOW-UP FROM THE PHASE 2 ELM-2 STUDY (EHA 2025) - P2 | "With longer follow-up, odronextamab demonstrated deep, durable responses in heavily pretreated pts with R/R FL from ELM-2; 80% of pts were responders, 92% of whom had a CR, and median DOCR was 32 mo with a median OS of >4 years. Robust efficacy was seen in pts with high-risk features, and odronextamab had a generally manageable safety profile. These results suggest that high CR rates with durability may confer long-term survival benefit in heavily pretreated pts with R/R FL and support the potential role of odronextamab in this setting."

Clinical • P2 data • Follicular Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Oncology • CD20

Zanubrutinib in Combination With Odronextamab for the Treatment of Patients With Richter's Transformation (clinicaltrials.gov) - P1 | N=23 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2026 ➔ Dec 2027 | Trial primary completion date: Nov 2026 ➔ Dec 2027

Enrollment open • Trial completion date • Trial primary completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome

ADVANCING NURSING KNOWLEDGE OF CD20-CD3 BISPECIFIC ANTIBODY TREATMENT FOR B-CELL NON-HODGKIN LYMPHOMA IN AUSTRALIA: A SCOPING REVIEW OF ADVERSE EVENTS TO INFORM PRACTICE (ICML 2025) - "Six BsAbs were identified: epcoritamab, glofitamab, imvotamab, mosunetuzumab, odronextamab and plamotamab...Supportive management, tocilizumab and corticosteroids were used for the treatment of CRS... BsAbs represent an effective treatment option in B-NHL with a unique side-effect profile. Some agents are now available through compassionate access programs in Australia and are increasingly encountered in routine practice around the world. This is the first published scoping review to synthesize evidence from clinical trials of BsAbs for nursing practice, informing nurses of the most common AEs and nursing led interventions for safe delivery and informed the development of an education package."

Adverse events • Review • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

BIOMARKER ANALYSES OF THE INFLAMMATORY PROFILE AND MRD IN PATIENTS WITH RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA VERSUS FOLLICULAR LYMPHOMA TREATED WITH ODRONEXTAMAB (ICML 2025) - P2 | "This biomarker analysis demonstrated T-cell activation, B-cell depletion, and substantial ctDNA reduction with odronextamab Tx, with a more pronounced inflammatory profile in R/R MZL versus FL (higher cytokine peaks, BL B-cell counts, and naïve T-cell proportions)."

Biomarker • Clinical • IO biomarker • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • CD20 • CD4 • CD8 • IFNG • IL6 • PD-1

LONGITUDINAL TARGETED ctDNA ANALYSIS TO ASSESS CD20 and BAFF MUTATIONS IN PATIENTS WITH RELAPSED/REFRACTORY FL OR DLBCL PROGRESSING ON ODRONEXTAMAB IN THE ELM-2 STUDY (ICML 2025) - P2 | "These data suggest that disease progression in pts with FL or DLBCL treated with odronextamab could be linked to emerging CD20 and BAFF mutations and show ctDNA analysis utility beyond MRD. CAPP-Seq detected more mutations versus WGS, possibly due to greater sequencing depth. Ongoing ctDNA analyses at earlier timepoints will help determine if CD20/BAFF variant detection before PD helps predict clinical outcomes."

Circulating tumor DNA • Clinical • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Lymphoma • Oncology • CD20 • CD22 • CD58 • CD79B

Long-term efficacy and survival outcomes with odronextamab in relapsed/refractory follicular lymphoma (R/R FL): 2-year follow-up from the Phase 2 ELM-2 study (ICML 2025) - No abstract available

Clinical • P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

COMPARATIVE EFFECTIVENESS OF ODRONEXTAMAB VERSUS REAL-WORLD SYSTEMIC THERAPIES USED IN AN EXTERNAL CONTROL ARM IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (ICML 2025) - P=N/A, P2 | "Compared with real-world 3L+ systemic therapies, odronextamab was associated with clinically meaningful and higher ORR and CR rates, longer OS and TTNTd, and favorable PFS. These results support the potential of odronextamab as an off-the-shelf, novel, and effective treatment that can improve outcomes in 3L+ R/R FL."

Clinical • HEOR • Real-world • Real-world evidence • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Indirect comparison of epcoritamab vs chemoimmunotherapy, mosunetuzumab, or odronextamab in follicular lymphoma. (PubMed, Blood Adv) - P1/2, P2 | "Epcoritamab also exhibited clinically relevant, numerically higher ORRs and demonstrated improved safety for CRS (grade ≥3) and ICANS vs mosunetuzumab or odronextamab. NCT03625037; NCT02500407; NCT03888105."

Journal • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

CD20×CD3 Bispecific Antibodies in B-NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research. (PubMed, Clin Transl Sci) - "Pivotal studies of four CD20 × CD3 bsAbs, mosunetuzumab, glofitamab, epcoritamab, and odronextamab, as monotherapy, have demonstrated robust responses with generally manageable safety profiles in patients with relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma after ≥ 2 lines of systemic therapy. This review provides a comprehensive overview of the clinical development of these four CD20 × CD3 bsAbs that have been investigated for the treatment of B-NHL, with a specific focus on translational assessments to select starting doses in first-in-human studies, management of CRS, application of modeling and simulation approaches to aid dose escalation and optimization/selection, and strategies used in the design of phase I-III clinical trials. By highlighting learnings and experiences from these four bsAbs assessed, which have not been summarized collectively elsewhere, we aim to promote more efficient study design for novel bsAbs in B-NHL..."

Journal • PK/PD data • Review • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Outcomes of odronextamab in non-Hodgkin lymphoma: A systematic review and meta-analysis. (ASCO 2025) - "This meta-analysis shows the good efficacy of odronextamab in the NHL with a modest safety profile. However, the meta-analysis is limited by a small sample size, necessitating the need for large randomized controlled trials in the future."

Retrospective data • Review • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • CD20

Long-term follow-up of the phase 2 ELM-2 study: Odronextamab for patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL). (ASCO 2025) - P2 | "With longer follow-up, odronextamab demonstrated durable responses in heavily pretreated pts with R/R FL from ELM-2, with robust efficacy in those with high-risk features, and a generally manageable safety profile. Overall, these compelling results support odronextamab as a potential off-the-shelf treatment option for pts with R/R FL."

Clinical • P2 data • Follicular Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Oncology • CD20

OLYMPIA-3: A Study to Compare How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Against Rituximab Combined With Chemotherapy, in Patients With Previously Untreated Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P3 | N=904 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2028 ➔ Apr 2029 | Trial primary completion date: Sep 2028 ➔ Mar 2028

Enrollment closed • Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Marginal zone lymphoma with anti-factor H IgM and atypical hemolytic uremic syndrome successfully treated with odronextamab. (PubMed, Haematologica) - "Not available."

Journal • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Nephrology • Oncology

Regeneron to Highlight Advances at ASCO with Phase 3 Adjuvant Libtayo (cemiplimab) CSCC Updates and Promising Early Blood Cancer Data with Linvoseltamab Combination (GlobeNewswire) - "Eighteen presentations will share the latest insights from ongoing research of approved and investigational treatment regimens across a range of difficult-to-treat cancers including non-melanoma and melanoma skin cancer, lung cancer, lymphoma and multiple myeloma...Notable presentations at ASCO on Regeneron’s oncology pipeline include detailed efficacy and safety findings from the Phase 3 C-POST trial evaluating the adjuvant use of the PD-1 inhibitor Libtayo in post-surgical high-risk cutaneous squamous cell carcinoma (CSCC). The results will be presented in an oral session on Saturday, May 31...Regeneron will debut results from two cohorts of the LINKER-MM2 trial...which will be featured in two rapid oral presentations on Monday, June 2...In addition, the results of a cooperative group study reporting on the primary analysis of a randomized Phase 2 trial of vidutolimod..."

Clinical data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Odronextamab Elicits Responses in Some With Lymphoma Following CAR-T (Cure Today) - P1 | N=200 | ELM-1 (NCT02290951) | Sponsor: Regeneron Pharmaceuticals | "Among some patients with relapsed/refractory diffuse large B-cell lymphoma whose disease progressed after CAR-T cell therapy, treatment with the bispecific antibody odronextamab has been associated with responses...Study results were published in Blood and evaluated among patients who were treated with intravenous odronextamab weekly for four cycles followed by maintenance until disease progression. In these 60 patients, after a median follow-up of 16.2 months, the objective response rate and complete response rate were 48.3% and 31.7%, while the median duration of response was 14.8 months; the median duration of complete response was not reached...the median progression-free survival and overall survival were 4.8 and 10.2 months, respectively."

P1 data • Diffuse Large B Cell Lymphoma

Regeneron's (REGN) Odronextamab Gains FDA Orphan Designation for Rare Lymphoma Treatment | REGN Stock News (Gurufocus) - "Regeneron Pharmaceuticals (REGN, Financial) has announced that its investigational drug, odronextamab, has been awarded orphan drug status by the U.S. Food and Drug Administration (FDA). This designation is specifically for the treatment of splenic marginal zone lymphoma, a rare type of cancer. The FDA's decision was published on their official website."

Orphan drug • Marginal Zone Lymphoma

Two strikes, base hit: odronextamab after CAR T cells in LBCL. (PubMed, Blood) - No abstract available

Journal

An evaluation of odronextamab for the treatment of multiple subtypes of relapsed/refractory B-cell non-hodgkin lymphoma. (PubMed, Expert Opin Biol Ther) - "High rates of severe infections remain a challenge with BsAbs, with further prophylactic efforts required to reduce the risk. Clinical trials of combination therapies with odronextamab are required to improve the utility of this BsAb across a wider range of settings and subtypes of B-NHL."

Journal • Review • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology