A Trial to Find Out if Odronextamab Combined With Lenalidomide is Safe and Works Better Than Rituximab Combined With Lenalidomide in Adult Participants With Follicular Lymphoma and Marginal Zone Lymphoma (OLYMPIA-5)

A Phase 3, Open Label, Randomized Study to Compare the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Combination With Lenalidomide Versus Rituximab in Combination With Lenalidomide in Relapsed/Refractory Participants With Follicular Lymphoma and Marginal Zone Lymphoma (OLYMPIA-5)

This study is researching an experimental drug called odronextamab (referred to as study drug), in combination with lenalidomide. The study is focused on participants who have one of two types of cancer: follicular lymphoma (FL) or marginal zone lymphoma (MZL) that has come back after treatment (called "relapsed"), or did not respond to treatment (called "refractory"). FL and MZL are subtypes of Non-Hodgkin 's lymphoma (NHL).

This study will be made up of two parts (Part 1 not randomized, Part 2 randomized - controlled).

The aim of Part 1 of the study is to see how safe and tolerable the study drug is when used in combination with lenalidomide, in participants with FL or MZL, and to determine the dose of the study drug to be used in Part 2 of this study. This combination is considered "first-in-human" as it has not been tested as a combination treatment in humans before.

The aim of Part 2, of the study is to assess how well the combination of the study drug and lenalidomide works compared to the combination of rituximab (called "the comparator drug") and lenalidomide. The combination of comparator drug and lenalidomide is the current standard-of-care treatment for relapsed/refractory FL and/or MZL. Standard-of-care means the usual medication expected and used when receiving treatment for a condition.

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

• What side effects may happen from taking the study drug in combination with lenalidomide
• 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)
• The impact from the study drug on quality-of-life and ability to complete routine daily activities

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Follicular Lymphoma; Relapsed/Refractory Marginal Zone Lymphoma (R/R MZL)
• Intervention / Treatment: Drug: Lenalidomide; Drug: Odronextamab; Drug: Rituximab

• Study Type: Interventional
• Enrollment (Estimated): 470
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • Liverpool Hospital
    • Waratah, New South Wales, Australia, 2298
      • Recruiting
      • Calvary Mater Newcastle
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Recruiting
      • Pindara Private Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Recruiting
      • Royal Hobart Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3121
      • Recruiting
      • Epworth Freemasons
• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University Vienna
  • Wels, Austria, 4600
    • Recruiting
    • Klinikum Wels-Grieskirchen
  • Osterreich
    • Linz, Osterreich, Austria, 4020
      • Recruiting
      • Ordensklinikum Linz
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • Recruiting
      • Kepler University Hospital
• Belgium
  • Antwerp, Belgium, 2060
    • Recruiting
    • Ziekenhuis Netwerk Antwerpen Stuivenberg
  • Brussels, Belgium, 1000
    • Recruiting
    • Institut Jules Bordet
  • Namur
    • Yvoir, Namur, Belgium, 5530
      • Recruiting
      • Centre Hospitalier Universitaire at Universite Catholique de Louvain Namur
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital
  • West-Vlaanderen
    • Roeselare, West-Vlaanderen, Belgium, 8800
      • Recruiting
      • Algemeen Ziekenhuis AZ Delta
• Brazil
  • Rio de Janeiro, Brazil, 20231050
    • Recruiting
    • Instituto Nacional de Cancer Jose Alencar Gomes da Silva
  • São Paulo, Brazil, 01308-050
    • Recruiting
    • Hospital Sírio Libanês
  • São Paulo, Brazil, 01321000
    • Recruiting
    • A Beneficencia Portuguesa de Sao Paulo, Oncology House
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40285-000
      • Recruiting
      • Hospital Sao Rafael
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • Recruiting
      • Hospital Sirio Libanes Brasilia
  • Paraná
    • Cascavel, Paraná, Brazil, 85806-300
      • Recruiting
      • Uopeccan Hospital do Cancer de Cascavel
    • Curitiba, Paraná, Brazil, 81520-060
      • Recruiting
      • Hospital Erasto Gaertner
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Recruiting
      • Hospital de Clinicas de Porto Alegre
    • Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
      • Recruiting
      • Centro Gaucho Integrado
  • São Paulo
    • Jaú, São Paulo, Brazil, 17210-080
      • Recruiting
      • Amaral Carvalho Hospital
• Czechia
  • Brno, Czechia, 62500
    • Recruiting
    • Fakultni nemocnice Brno
  • Prague, Czechia, 12808
    • Recruiting
    • Vseobecna fakultni nemocnice v Praze
  • Prague, Czechia, 10034
    • Recruiting
    • University Hospital Královské Vinohrady
  • East Bohemia
    • Hradec Králové, East Bohemia, Czechia, 50005
      • Recruiting
      • University hospital Hradec Králové
• France
  • Avignon, France, 84000
    • Recruiting
    • Centre hospitalier d'Avignon
  • Montpellier, France, 34290
    • Recruiting
    • Centre Hospitalier Universitaire (CHU) Montpellier
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint Louis
  • Paris, France, 75571
    • Recruiting
    • Assistance Publique-Hopitaux de Paris (AP-HP)
  • Saint-Cloud, France, 92210
    • Recruiting
    • Institut Curie
  • Bouches Du Rhone
    • Marseille, Bouches Du Rhone, France, 13009
      • Recruiting
      • Institut Paoli-Calmettes
  • Brittany Region
    • Rennes, Brittany Region, France, 35033
      • Recruiting
      • CHU de Rennes
  • Centre-Val de Loire
    • Tours, Centre-Val de Loire, France, 37044
      • Recruiting
      • Centre Hospitalier Régional Universitaire de Tours
  • Gironde
    • Bordeaux, Gironde, France, 33077
      • Recruiting
      • Polyclinique Bordeaux Nord Aquitaine
    • Pessac, Gironde, France, 33600
      • Recruiting
      • Centre Francois Magendie
  • Nord
    • Lille, Nord, France, 5900
      • Recruiting
      • Hopital Saint Vincent-de-Paul
  • Normandy
    • Rouen, Normandy, France, 76038
      • Recruiting
      • Centre Henri Becquerel
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44093
      • Recruiting
      • Nantes University Hospital
  • Savoie
    • Chambéry, Savoie, France, 73000
      • Recruiting
      • Centre Hospitalier Metropole Savoie
  • Île-de-France Region
    • Argenteuil, Île-de-France Region, France, 95100
      • Recruiting
      • Hopital Victor Dupouy Argenteuil
    • Bobigny, Île-de-France Region, France, 93000
      • Recruiting
      • Avicenne Hospital
    • Villejuif, Île-de-France Region, France, 94800
      • Recruiting
      • Gustave Roussy
• Germany
  • Halle, Germany, 6120
    • Recruiting
    • University Hospital Halle Saale
  • Kiel, Germany, 24116
    • Recruiting
    • Stadtisches Krankenhaus Kiel
  • Neuss, Germany, 41462
    • Recruiting
    • MVZ fuer Haematologie und Onkologie Rhein-Kreis GmbH
  • Baden-Wurttemberg
    • Mutlangen, Baden-Wurttemberg, Germany, 73557
      • Recruiting
      • Stauferklinikum
    • Stuttgart, Baden-Wurttemberg, Germany, 70376
      • Recruiting
      • Robert-Bosch-Krankenhaus
  • Bavaria
    • Munich, Bavaria, Germany, 80337
      • Recruiting
      • LMU Klinikum
    • Munich, Bavaria, Germany, 81675
      • Recruiting
      • TUM Fakultat fur Medizin - Klinikum Rechts der Isar
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 15236
      • Recruiting
      • Clinic Frankfurt (Oder)
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Recruiting
      • Universitatsmedizin der Johannes-Gutenberg Universitat Mainz
• Israel
  • Ashdod, Israel, 7747629
    • Recruiting
    • Assuta Ashdod Medical Center
  • Jerusalem, Israel, 91200
    • Recruiting
    • Hadassah Medical Center
  • Nahariya, Israel, 2210001
    • Recruiting
    • Galilee Medical Center
  • Petah Tikva, Israel, 49100
    • Recruiting
    • Rabin Medical Center
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Recruiting
    • The Tel Aviv Sourasky Medical Center
  • Tel Aviv, Israel, 6971028
    • Recruiting
    • Assuta Medical Centers
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • University of Bologna Dipartimento di Medicina Specialistica Diagnostica e Sperimentale
  • Brescia, Italy, 25123
    • Recruiting
    • Azienda Ospedaliera Spedali Civili di Brescia
  • Milan, Italy, 20122
    • Recruiting
    • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
  • Milan, Italy, 20141
    • Recruiting
    • Istituto Europeo Di Oncologia
  • Milan, Italy, 20162
    • Recruiting
    • ASST Grande Ospedale Metropolitano Niguarda - Main Address
  • Modena, Italy, 41124
    • Recruiting
    • A.O.U. di Modena
  • Naples, Italy, 80131
    • Recruiting
    • Federico II University
  • Novara, Italy, 28100
    • Recruiting
    • Aou Maggiore Della Carita
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione IRCCS Policlinico San Matteo
  • Perugia, Italy, 06132
    • Recruiting
    • Azienda Ospedaliera di Perugia
  • Ravenna, Italy, 48121
    • Recruiting
    • Ospedale Santa Maria delle Croci
  • Udine, Italy, 33100
    • Recruiting
    • Santa Maria della Misericordia
  • Forli-Cesena
    • Meldola, Forli-Cesena, Italy, 47014
      • Recruiting
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Genova
    • Genoa, Genova, Italy, 16132
      • Recruiting
      • Ospedale Policlinico San Martino IRCCS
  • Monza E Brianza
    • Monza, Monza E Brianza, Italy, 20900
      • Recruiting
      • S Gerardo Hospital
  • Piedmont
    • Turin, Piedmont, Italy, 10126
      • Recruiting
      • A.O.U. Città della Salute e Della Scienza di Torino
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Recruiting
      • Centro Di Riferimento Oncologico (CRO), Aviano, National Cancer Institute
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Recruiting
      • Candiolo Cancer Institute, FPO, IRCCS
• Malaysia
  • Johor
    • Johor Bahru, Johor, Malaysia, 80100
      • Recruiting
      • Hospital Sultanah Aminah Jhor Bahru
  • Negeri / Wilayah Persekutuan
    • Kuala Lumpur, Negeri / Wilayah Persekutuan, Malaysia, 50603
      • Recruiting
      • University of Malaya Medical Centre
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Recruiting
      • Hospital Queen Elizabeth
  • Selangor
    • Ampang, Selangor, Malaysia, 68000
      • Recruiting
      • Hospital Ampang
    • Subang Jaya, Selangor, Malaysia, 47500
      • Recruiting
      • Subang Jaya Medical Center
• Poland
  • Bydgoszcz, Poland, 85-168
    • Withdrawn
    • Szpital Uniwersytecki Nr2 Bydgoszcz
  • Katowice, Poland, 40-519
    • Recruiting
    • Pratia Onkologia Katowice
  • Lodz, Poland, 93-513
    • Recruiting
    • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Mikolaja Kopernika w Lodzi (Copernicus Memorial Hospital)
  • Warsaw, Poland, 02-781
    • Recruiting
    • Narodowy Instytut Onkologii
  • Lower Silesian Voivodeship
    • Wałbrzych, Lower Silesian Voivodeship, Poland, 58-309
      • Recruiting
      • Specjalistyczny Szpital im A. Sokolowskiego w Walbrzychu
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-367
      • Recruiting
      • Uniwersytecki Szpital Kliniczny
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-090
      • Recruiting
      • Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie, Centrum Innowacyjnych Terapii
  • Malopolska
    • Krakow, Malopolska, Poland, 30-510
      • Recruiting
      • Pratia MCM Krakow
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-952
      • Recruiting
      • Uniwersyteckie Centrum Kliniczne
  • Wielkopolska
    • Poznan, Wielkopolska, Poland, 60185
      • Completed
      • Pratia Poznan Medical Center
    • Skorzewo, Wielkopolska, Poland, 60185
      • Recruiting
      • Aidport
• South Korea
  • Busan, South Korea, 49241
    • Recruiting
    • Pusan National University Hospital
  • Busan, South Korea, 47392
    • Recruiting
    • Inje University Busan Paik Hospital
  • Daegu, South Korea, 42415
    • Withdrawn
    • Yeyungnam University Medical Center
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 3080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 07345
    • Recruiting
    • Yeouido St. Marys Hospital
  • Seoul, South Korea, 03722
    • Recruiting
    • Yonsei University Health System
  • Seoul, South Korea, 137-701
    • Recruiting
    • Seoul St Marys Hospital
  • Ulsan, South Korea, 44033
    • Recruiting
    • Ulsan University Hospital
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, South Korea, 16247
      • Recruiting
      • St. Vincents Hospital - The Catholic University of Korea
  • Jeollabuk
    • Jeonju, Jeollabuk, South Korea, 54907
      • Recruiting
      • Jeonbuk National University Hospital
  • Namdong-Gu
    • Incheon, Namdong-Gu, South Korea, 21565
      • Recruiting
      • Gachon University Gil Medical Center
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08041
    • Recruiting
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 08035
    • Recruiting
    • University Hospital Vall d'Hebron
  • Granada, Spain, 18014
    • Recruiting
    • Hospital Virgen De Las Nieves De Granada
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario HM Sanchinarro
  • Madrid, Spain, 28040
    • Recruiting
    • Fundacion Jimenez Diaz University Hospital
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario12 de Octubre
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Universitario de Salamanca
  • Seville, Spain, 41013
    • Recruiting
    • University Hospital Virgen del Rocio
  • Valencia, Spain, 46009
    • Recruiting
    • Instituto Valenciano de Oncologia
  • Valencia, Spain, 46017
    • Recruiting
    • University Hospital Doctor Peset
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Recruiting
      • University Hospital of Santiago de Compostela
  • Balearic Islands
    • Palma, Balearic Islands, Spain, 07120
      • Recruiting
      • Son Espases University Hospital
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Recruiting
      • Institut Catala d'Oncologia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Recruiting
      • Hospital Universitario Marques de Valdecilla
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Recruiting
      • Hospital Universitario Quironsalud Madrid
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Recruiting
      • Hospital Universitario Central de Asturias
• Taiwan
  • Changhua, Taiwan, 500-06
    • Recruiting
    • Changhua Christian Hospital
  • Changhua, Taiwan, 50008
    • Recruiting
    • Show Chwan Memorial Hospital
  • Kaohsiung City, Taiwan, 83301
    • Recruiting
    • Chang Gung Memorial Hospital Kaohsiung
  • Kaohsiung City, Taiwan, 80756
    • Recruiting
    • Kaohsiung Medical University Hospital
  • New Taipei City, Taiwan, 23561
    • Recruiting
    • Taipei Medical University - Shuang Ho Hospital
  • Tainan, Taiwan, 701
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 11490
    • Recruiting
    • Tri-Service General Hospital
  • Taipei, Taiwan, 116
    • Recruiting
    • Taipei Municipal Wan Fang Hospital
  • Taoyuan City, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital
  • Chiayi County
    • Buzi, Chiayi County, Taiwan, 613
      • Recruiting
      • Chang Gung Medical Foundation Chia Yi Branch
• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Sriraj Hospital
  • Chiang Mai, Thailand, 50200
    • Recruiting
    • Chiang Mai University
  • Krung Thep Maha Nakhon [Bangko]
    • Bangkok, Krung Thep Maha Nakhon [Bangko], Thailand, 10330
      • Recruiting
      • Chulalongkorn University
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34093
    • Recruiting
    • Istanbul University, Istanbul Medical Faculty
  • Izmir, Turkey (Türkiye), 35100
    • Recruiting
    • Ege University
  • Izmir, Turkey (Türkiye), 35340
    • Recruiting
    • Dokuz Eylul University
  • Sakarya, Turkey (Türkiye), 54290
    • Recruiting
    • Sakarya University Medical Faculty
  • Samsun, Turkey (Türkiye), 55270
    • Recruiting
    • Ondokuz Mayıs University
  • Zonguldak, Turkey (Türkiye), 67600
    • Recruiting
    • Zonguldak Bülent Ecevit University
  • Ankara
    • Mamak, Ankara, Turkey (Türkiye), 06620
      • Recruiting
      • Ankara University Faculty of Medicine
    • Yenimahalle, Ankara, Turkey (Türkiye), 06200
      • Recruiting
      • Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
  • Central Anatolia
    • Ankara, Central Anatolia, Turkey (Türkiye), 06100
      • Recruiting
      • Gazi University
  • Mersin
    • Mezitli, Mersin, Turkey (Türkiye), 33200
      • Recruiting
      • VM Medical Park Mersin Hospital
  • Suleymanpasa
    • Tekirdağ, Suleymanpasa, Turkey (Türkiye), 59100
      • Recruiting
      • Tekirdag Namik Kemal University Hospital
• United Kingdom
  • Great Yarmouth, United Kingdom, NR31 6LA
    • Recruiting
    • James Paget University Hospitals NHS Foundation Trust
  • Romford, United Kingdom, RM7 0AG
    • Recruiting
    • Barking, Havering and Redbridge University Hospitals NHS Trust
  • Warwick, United Kingdom, CV34 5BW
    • Recruiting
    • South Warwickshire NHS Foundation Trust
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Recruiting
      • Royal Cornwall Hospitals NHS Trust
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • Recruiting
      • Derriford Hospital and the Royal Eye Infirmary
  • Dorset
    • Bournemouth, Dorset, United Kingdom, BH7 7DW
      • Recruiting
      • University Hospitals Dorset
  • Hampshire
    • Salisbury, Hampshire, United Kingdom, SP6 2ND
      • Recruiting
      • Salisbury Foundation Trust
  • Middlesex
    • Uxbridge, Middlesex, United Kingdom, UB8 3NN
      • Recruiting
      • The Hillingdon Hospital
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Recruiting
      • The Royal Marsden NHS Foundation Trust
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • David Geffen School of Medicine at UCLA
  • Florida
    • Plantation, Florida, United States, 33322
      • Recruiting
      • Boca Raton Clinical Research (BRCR) Global
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University and Comprehensive Cancer Center
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Recruiting
      • Hattiesburg Clinic
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Dartmouth Cancer Center
  • New York
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook University Hospital
    • Westbury, New York, United States, 11590
      • Withdrawn
      • Clinical Research Alliance Inc
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • Recruiting
      • Prohealth Care Inc

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Local histologic confirmation of FL grade 1-3a or MZL (nodal, splenic, or extra nodal MZL) as assessed by the investigator, as described in the protocol.
2. Must have refractory disease or relapsed after at least 1 prior line (with a duration of at least 2 cycles) of systemic chemo-immunotherapy or immunotherapy. Prior systemic therapy should have included at least one anti-Cluster of Differentiation 20 (CD20) monoclonal antibody and participant should meet indication for treatment, as described in the protocol.
3. Have measurable disease on cross sectional imaging documented by diagnostic Computed Tomography [CT], or Magnetic Resonance Imaging [MRI] imaging, as described in the protocol.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Adequate hematologic and organ function, as described in the protocol.

6. All study participants must:

   1. Have an understanding that lenalidomide could have a potential teratogenic risk.
   2. Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of lenalidomide.
   3. Agree not to share study medication with another person.
   4. Agree to be counseled about pregnancy precautions and risk of fetal exposure associated with lenalidomide.

Key Exclusion Criteria:

1. Primary Central Nervous System (CNS) lymphoma or known involvement (either current or prior history of CNS involvement) by non-primary CNS NHL, as described in the protocol.
2. Participants with current or past histological evidence of high-grade or diffuse large B-cell lymphoma, or any histology other than FL grade 1-3a or MZL.
3. History of or current relevant CNS pathology, as described in the protocol.
4. A malignancy other than NHL (inclusion diagnosis) unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer treated with hormone therapy or local radiotherapy (ie, pellets), cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated.
5. 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.
6. Allergy/hypersensitivity to study drugs or excipients. as described in the protocol.
7. Active infection as defined in the protocol.

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: Rituximab+Lenalidomide; In part 2 only, 1:1 randomized participants with R/R lymphoma (FL and ML), will receive rituximab in combination with lenalidomide (R2) followed by lenalidomide monotherapy.	Drug: Lenalidomide; Administered per the protocol; Other Names: REVLIMID; Drug: Rituximab; Administered per the protocol; Other Names: Rituxan
Experimental: Odronextamab+Lenalidomide; In part 1 (safety run-in), participants with R/R indolent lymphoma (FL and MZL), will receive odronextamab in combination with lenalidomide. In part 2, 1:1 randomized participants with R/R indolent lymphoma (FL/MZL), will receive odronextamab in combination with lenalidomide.	Drug: Lenalidomide; Administered per the protocol; Other Names: REVLIMID; Drug: Odronextamab; Administered per the protocol; Other Names: REGN1979; Ordspono

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of TEAEs for odronextamab in combination with lenalidomide	Part 1	Up to 2 years
Incidence of Dose Limiting Toxicities (DLTs) for odronextamab in combination with lenalidomide	Part 1	Up to 35 days
Incidence of Treatment Emergent Adverse Events (TEAEs) for odronextamab in combination with lenalidomide	Part 1	Up to 2 years
Progression-Free Survival (PFS) as assessed by Independent Central Review (ICR) in participants with R/R FL and participants with indolent lymphoma	Part 2	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Part 2	Up to 5 years
BOR as assessed by ICR	Part 2	Up to 30 months
Odronextamab concentrations in serum	Part 1 and Part 2	Up to 30 months
PFS as assessed by investigator review	Part 1 and Part 2	Up to 5 years
EFS as assessed by local investigator review	Part 2	Up to 5 years
DOR as assessed by ICR	Part 2	Up to 5 years
Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2	Part 2	Up to 2 years
Severity of TEAEs for odronextamab in combination with lenalidomide versus R2	Part 2	Up to 2 years
Overall change in patient reported outcomes (PROs) as measured by scores of European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQC30)	Part 2 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.	Up to 5 years
Overall change in PROs as measured by scores of Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)	Part 2 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.	Up to 5 years
Overall change in PROs as measured by scores of EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)	Part 2 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".	Up to 5 years
Time To Next anti-lymphoma Treatment (TTNT)	Part 2	Up to 5 years
Incidence of Anti-drug Antibodies (ADA) to odronextamab	Part 1 and Part 2	Up to 30 months
Magnitude of ADAs to odronextamab	Part 1 and Part 2	Up to 30 months
Best Overall Response (BOR) as assessed by investigator review	Part 1 and Part 2	Up to 30 months
Duration of Response (DOR) as assessed by investigator review	Part 1 and Part 2	Up to 5 years
Complete Response (CR) as assessed by ICR	Part 2	Up to 30 months
Event Free Survival (EFS) as assessed by ICR	Part 2	Up to 5 years
Change from first assessment in Patient Global Impression on Severity (PGIS)	Part 2 The PGIS includes a single-item to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. Patients will choose the response that best describes the severity of their overall cancer symptoms with options on a 5-point scale ranging from 1 (No symptoms) to 4 (Very Severe).	Up to 5 years
Change from first assessment in Patient Global Impression on Change (PGIC)	Part 2 The PGIC item includes a single-item to assess how a patient perceives their overall change in health status since the start of study treatment. Patients will choose from response options on a 7-point scale ranging from 1 (Much Better) to 7 (Much worse); 1- Much Better, 2-Moderately Better, 3-A Little Better, 4-About the Same, 5-A Little Worse, 6-Moderately Worse, 7-Much Worse.	Up to 5 years
Change from first assessment in the Global Population item 5 (GP5) items of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire	Part 2 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).	Up to 5 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): December 28, 2023
• Primary Completion (Estimated): January 23, 2029
• Study Completion (Estimated): January 23, 2029

Study Registration Dates

• First Submitted: November 20, 2023
• First Submitted That Met QC Criteria: November 20, 2023
• First Posted (Actual): November 28, 2023

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Odronextamab; Non-Hodgkin lymphomas; Relapsed/Refractory Follicular Lymphoma; Indolent lymphomas; Relapsed/Refractory Marginal Zone Lymphoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Rituximab
• Other Study ID Numbers: R1979-ONC-22102; 2022-503092-28-00 (Ctis: 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