A Trial to Learn How Effective and Safe Odronextamab is Compared to Standard of Care for Adult Participants With Previously Treated Aggressive B-cell Non-Hodgkin Lymphoma (OLYMPIA-4)

A Phase 3, Randomized, Open Label Study Evaluating the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 x Anti-CD3 Bispecific Antibody, Versus Standard of Care Therapy in Participants With Relapsed/Refractory Aggressive B-cell Non-Hodgkin Lymphoma (OLYMPIA-4)

This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on patients with previously treated aggressive B-cell non-Hodgkin lymphoma whose cancer has stopped responding to treatment (also known as 'refractory') or has returned (also known as 'relapsed'). The aim of the study is to see how safe, tolerable and effective the study drug is when given alone.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug versus Standard of Care (SOC)
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)
• Comparing the impact from the study drug versus SOC on quality-of-life and ability to complete routine daily activities

Study Overview

• Status: Active, not recruiting
• Conditions: B-Cell Non-Hodgkin Lymphoma (B-NHL)
• Intervention / Treatment: Drug: Odronextamab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide; Drug: Rituximab; Drug: Dexamethasone; Drug: Cisplatin; Drug: Cytarabine; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 216
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina, X5000JHQ
    • Sanatorio Allende
  • Córdoba, Argentina, X5016KEH
    • Hospital Privado Universitario De Cordoba
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1199ABB
      • Hospital Italiano de Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1114AAN
      • Fundaleu - Fundacion Para Combatir La Leucemia
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 1118
      • Hospital Aleman
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 1280
      • Hospital Britanico de Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 1426
      • Instituto Alexander Fleming
    • La Plata, Buenos Aires, Argentina, B1900AUR
      • Hospital Italiano de La Plata
    • San Juan Bautista, Buenos Aires, Argentina, B1888AAE
      • Hospital Alta Complejidad El Cruce
• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Olivia Newton John Cancer Wellness & Research Centre
• Brazil
  • Rio de Janeiro, Brazil, 20231050
    • Instituto Nacional de Cancer Jose Alencar Gomes da Silva
  • São Paulo, Brazil, 01308-050
    • Hospital Sirio Libanes
  • São Paulo, Brazil, 08270-070
    • Casa de Saude Santa Marcelina
  • São Paulo, Brazil, 01321000
    • A Beneficencia Portuguesa de Sao Paulo, Oncology House
  • São Paulo, Brazil, 04501-000
    • Instituto D'Or de Pesquisa e Ensino
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas, Faculty of Medicine, University of Sao Paulo
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40050-410
      • Hospital Santa Izabel - Santa Casa de Misericórdia da Bahia
    • Salvador, Estado de Bahia, Brazil, 41950-640
      • Ensino e Terapia de Inovacao Clinica Amo (Etica)
    • Salvador, Estado de Bahia, Brazil, 40285-000
      • Hospital Sao Rafael
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • Hospital Sirio Libanes Brasilia
  • Paraná
    • Cascavel, Paraná, Brazil, 85806-300
      • Uopeccan Hospital do Cancer de Cascavel
    • Curitiba, Paraná, Brazil, 81520-060
      • Hospital Erasto Gaertner
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital De Clinicas De Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
      • Centro Gaucho Integrado
  • São Paulo
    • Jaú, São Paulo, Brazil, 17210-080
      • Amaral Carvalho Hospital
• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 7500921
      • Fundacion Arturo Lopez Perez
    • Santiago, Santiago Metropolitan, Chile, 7650620
      • Clínica Alemana de Santiago
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050034
      • Hospital Pablo Tobon Uribe
  • Valle del Cauca Department
    • Cali, Valle del Cauca Department, Colombia, 760042
      • Clinica Imbanaco
• Hungary
  • Budapest, Hungary, 1088
    • Semmelweis University
  • Baranya
    • Pécs, Baranya, Hungary, 7624
      • University of Pecs
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary, 4032
      • Debreceni Egyetem
• Malaysia
  • Johor
    • Johor Bahru, Johor, Malaysia, 80100
      • Hospital Sultanah Aminah Jhor Bahru
  • Kuala Lumpur
    • Kuala Lumpur, Kuala Lumpur, Malaysia, 59100
      • University Malaya Medical Centre
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Hospital Queen Elizabeth
  • Selangor
    • Kuala Lumpur, Selangor, Malaysia, 68000
      • Hospital Ampang
    • Subang Jaya, Selangor, Malaysia, 47500
      • Subang Jaya Medical Center
• Romania
  • Bucharest
    • Bucharest, Bucharest, Romania, 030141
      • Coltea Clinical Hospital
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Ion Chiricuta Oncology Institute
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital Singapore
• South Korea
  • Busan, South Korea, 49201
    • Dong-A University Hospital
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Daegu, South Korea, 42601
    • Keimyung University Dongsan Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 07345
    • Yeouido St. Marys Hospital
  • Seoul, South Korea, 06591
    • Seoul St Marys Hospital
  • Ulsan, South Korea, 44033
    • Ulsan University Hospital
  • Gyeonggi-do
    • Gyeonggi-do, Gyeonggi-do, South Korea, 10408
      • National Cancer Center
    • Suwon, Gyeonggi-do, South Korea, 16247
      • St. Vincent Hospital - The Catholic University of Korea
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, South Korea, 50612
      • Pusan National University Yangsan Hospital
  • Jeollabuk-do
    • Jeonju, Jeollabuk-do, South Korea, 54907
      • Jeonbuk National University Hospital
  • Namdong-Gu
    • Incheon, Namdong-Gu, South Korea, 21565
      • Gachon University Gil Medical Center
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra- Pamplona
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncologia
  • Balearic Islands
    • Palma, Balearic Islands, Spain, 07120
      • Hospital Universitari Son Espases
• Taiwan
  • Changhua, Taiwan, 500-06
    • Changhua Christian Hospital
  • Changhua, Taiwan, 50008
    • Show Chwan Memorial Hospital
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Hospital
  • Kaohsiung City, Taiwan, 83301
    • Chang Gung Memorial Hospital Kaohsiung
  • Taichung, Taiwan, 40705
    • Taichung General Veterans Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11490
    • Tri-Service General Hospital
  • Hunan Province
    • Taoyuan, Hunan Province, Taiwan, 33305
      • Chang Gung Memorial Hospital - Linkou Branch
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn University
  • Bangkok, Thailand, 10700
    • Sriraj Hospital
  • Chiang Mai, Thailand, 50200
    • Chiang Mai University
  • Khon Kaen, Thailand, 40002
    • Khon Kaen University
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Sbu Dr.A.Y. Ankara Onkoloji Suam
  • Istanbul, Turkey (Türkiye), 34365
    • VKV American Hopital
  • Istanbul, Turkey (Türkiye), 34418
    • Istanbul University
  • Izmir, Turkey (Türkiye), 35100
    • Ege University
  • Sakarya, Turkey (Türkiye), 54290
    • Sakarya University Medical Faculty
  • Samsun, Turkey (Türkiye), 55270
    • Ondokuz Mayıs University
  • Zonguldak, Turkey (Türkiye), 67600
    • Zonguldak Bülent Ecevit University
  • Ankara
    • Mamak, Ankara, Turkey (Türkiye), 06620
      • Ankara University Faculty of Medicine
  • Central Anatolia
    • Ankara, Central Anatolia, Turkey (Türkiye), 06100
      • Gazi University
  • Mersin
    • Mezitli, Mersin, Turkey (Türkiye), 33200
      • VM Medical Park Mersin Hospital
  • Suleymanpasa
    • Tekirdağ, Suleymanpasa, Turkey (Türkiye), 59100
      • Tekirdag Namik Kemal University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Histologically proven aggressive B-NHL, as described in the protocol. Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed
2. Have primary refractory or relapse 12 months or less (≤) from initiation of frontline therapy Only patients who received 1 prior line of therapy containing an anti-Cluster of Differentiation 20 (CD20) antibody and anthracycline are allowed for enrollment
3. Have measurable disease with at least one nodal lesion with longer diameter (LDi) greater than 1.5 cm or at least one extranodal lesion with LDi greater than 1.0 cm, documented by diagnostic imaging (computed tomography [CT] or magnetic resonance imaging [MRI])
4. Intent to proceed to autologous stem cell transplant (ASCT), as described in the protocol
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
6. Adequate hematologic and organ function.

Key Exclusion Criteria:

1. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL, as described in the protocol
2. History of or current relevant CNS pathology, as described in the protocol
3. A malignancy other than NHL unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated
4. Any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, as described in the protocol
5. Wash-out period from prior anti-lymphoma treatments and infections, as described in the protocol
6. Allergy/hypersensitivity to study drug, or excipients.

NOTE: Other protocol defined inclusion / exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Odronextamab; Participants will receive odronextamab monotherapy.	Drug: Odronextamab; Administered by intravenous (IV) infusion; Other Names: R1979
Active Comparator: Standard Of Care; Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab [ICE ± R], or dexamethasone, cisplatin, cytarabine ± rituximab [DHAP ± R], or gemcitabine, dexamethasone, cisplatin ± rituximab [GDP ± R]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR).	Drug: Ifosfamide; Administered by IV infusion, as part of the ICE ± R salvage therapy; Other Names: Ifex; Drug: Carboplatin; Administered by IV infusion, as part of the ICE ± R salvage therapy; Other Names: Paraplatin; Drug: Etoposide; Administered by IV infusion, as part of the ICE ± R salvage therapy; Other Names: Etopophos; Drug: Rituximab; Administered by IV infusion, as part of the ICE ± R, or DHAP ± R, or GDP ± R salvage therapy.; Other Names: Rituxan; Drug: Dexamethasone; Administered by IV, or orally (PO) as part of the DHAP ± R, or GDP ± R salvage therapy.; Other Names: Decadron; Drug: Cisplatin; Administered by IV infusion, as part of the DHAP ± R or GDP +/-R salvage therapy.; Other Names: Platinol; Drug: Cytarabine; Administered by IV infusion, as part of the DHAP ± R salvage therapy.; Other Names: Cytosar-U; Drug: Gemcitabine; Administered by IV infusion, as part of the GDP ± R salvage therapy.; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event-free survival (EFS) as assessed by independent central review (ICR)	Assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFS as assessed by local investigator		Assessed up to 3 years
PFS as assessed by local investigator		Assessed up to 3 years
BOR as assessed by local investigator		Assessed up to 6 months
CR as assessed by local investigator		Assessed up to 6 months
DOR assessed by local investigator		Assessed up to 3 years
Overall survival (OS)		Assessed up to 3 years
Incidence of treatment-emergent adverse events (TEAEs)		Assessed up to 1 year
Severity of TEAEs		Assessed up to 1 year
Odronextamab concentrations in serum		Assessed up to 6 months
Measurable residual disease (MRD) status		Assessed up to 6 months
Overall change in physical functioning as measured by scores of the physical function scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30)	The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a global health status (GHS)/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.	Assessed up to 3 years
Incidence of anti-drug antibodies (ADAs) to odronextamab over the study duration		Assessed up to 6 months
Titers of ADAs to odronextamab over the study duration		Assessed up to 6 months
Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration		Assessed up to 6 months
Overall change in score of the Global Population item 5 (GP5) of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire	A single item GP5 of the validated FACT-G questionnaire will be used to assess from the participant perspective the overall impact of treatment side-effect. The question item is on a 5-point scale ranging from "not at all" (0) to "very much" (4).	Assessed up to 3 years
Progression free survival (PFS) as assessed by ICR		Assessed up to 3 years
Best overall response (BOR) as assessed by ICR		Assessed up to 6 months
Complete response (CR) as assessed by ICR		Assessed up to 6 months
Duration of response (DOR) assessed by ICR		Assessed up to 3 years
Overall change in patient-reported outcomes (PROs), as measured by scores of the EORTCQLQ- C30	The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.	Assessed up to 3 years
Overall change in PROs, as measured by scores of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-LymS)	The FACT-Lym lymphoma subscale (LymS) includes 15 items to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). Higher scores are associated with a worse quality of life.	Assessed up to 3 years
Overall change in PROs, as measured by scores of the EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)	The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state".	Assessed up to 3 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• OLYMPIA

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): May 29, 2028
• Study Completion (Estimated): May 29, 2029

Study Registration Dates

• First Submitted: December 29, 2023
• First Submitted That Met QC Criteria: January 18, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Odronextamab; Anti-CD20 × anti-CD3 bispecific antibody; Non-Hodgkin lymphomas (NHLs); B-Cell Non-Hodgkin Lymphoma (B-NHL); Aggressive NHL; Relapsed/Refractory NHL
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Sulfonic Acids; Sulfur Acids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nucleosides; Pregnadienetriols; Arabinonucleosides; Platinum Compounds; Antibodies, Monoclonal, Murine-Derived; Oxazines; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Cyclophosphamide; Rituximab; Gemcitabine; Dexamethasone; Cytarabine; Etoposide; Carboplatin; Cisplatin; Ifosfamide; Calcium Dobesilate; etoposide phosphate
• Other Study ID Numbers: R1979-HM-2299; 2022-502783-21-00 (Registry Identifier: EUCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes