A Trial to Learn 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

Phase 3

Recruiting

• Conditions: Marginal Zone Lymphoma (MZL); Relapsed/Refractory Follicular Lymphoma
• Interventions: Drug: Odronextamab; Drug: Lenalidomide; Drug: Rituximab

• Registration Number: NCT06149286
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

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 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 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-20
• Study First Submitted QC: 2023-11-20
• Study First Posted: 2023-11-28
• Study Start: 2023-12-28
• Status Verified: 2025-04
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-13
• Primary Completion: 2029-01-23
• Study Completion: 2029-01-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 470

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 histological evidence of transformation to a 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 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Odronextamab+Lenalidomide	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 indolent lymphoma (FL/MZL), will receive odronextamab in combination with lenalidomide.
Odronextamab+Lenalidomide	Odronextamab	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 indolent lymphoma (FL/MZL), will receive odronextamab in combination with lenalidomide.
Rituximab+Lenalidomide	Rituximab	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.
Rituximab+Lenalidomide	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.

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) as assessed by independent central review (ICR) in participants with R/R FL and participants with indolent lymphoma	Up to 5 years	Part 2
Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with lenalidomide	Up to 35 days	Part 1
Incidence of treatment emergent adverse events (TEAEs) for odronextamab in combination with lenalidomide	Up to 2 years	Part 1
Severity of TEAEs for odronextamab in combination with lenalidomide	Up to 2 years	Part 1

Secondary Outcome Measures

Name	Time	Method
Incidence of anti-drug antibodies (ADA) to odronextamab over the study duration	Up to 30 months	Part 1 and Part 2
Complete response (CR) as assessed by ICR	Up to 30 months	Part 2
Overall survival (OS)	Up to 5 years	Part 2
Event free survival (EFS) as assessed by ICR	Up to 5 years	Part 2
Odronextamab concentrations in serum	Up to 30 months	Part 1 and Part 2
Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2	Up to 2 years	Part 2
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)	Up to 5 years	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.
Overall change in score of the global population item 5 (GP5) items of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire	Up to 5 years	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).
Titer of ADAs to odronextamab over the study duration	Up to 30 months	Part 1 and Part 2
Incidence of neutralizing antibodies (NAbs) to odronextamab over the study duration	Up to 30 months	Part 1 and Part 2
Best overall response (BOR) as assessed by investigator review	Up to 30 months	Part 1 and Part 2
BOR as assessed by ICR	Up to 30 months	Part 2
DOR as assessed by ICR	Up to 5 years	Part 2
Time to next anti-lymphoma treatment (TTNT)	Up to 5 years	Part 2
Severity of TEAEs for odronextamab in combination with lenalidomide versus R2	Up to 2 years	Part 2
Duration of response (DOR) as assessed by investigator review	Up to 5 years	Part 1 and Part 2
PFS as assessed by investigator review	Up to 5 years	Part 1 and Part 2
EFS as assessed by local investigator review	Up to 5 years	Part 2
Overall change in PROs as measured by scores of Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)	Up to 5 years	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.
Overall change in PROs as measured by scores of Patient Global Impression on Change (PGIC)	Up to 5 years	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.
Overall change in PROs as measured by scores of EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)	Up to 5 years	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".
Overall change in PROs as measured by scores of Patient Global Impression on Severity (PGIS)	Up to 5 years	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).

Trial Locations

Locations (142)

Klinikum Wels Grieskirchen; 🇦🇹 Wels, Austria

Institut Jules Bordet; 🇧🇪 Brussels, Belgium

David Geffen School of Medicine at UCLA; 🇺🇸 Los Angeles, California, United States

Boca Raton Clinical Research (BRCR) Global; 🇺🇸 Plantation, Florida, United States

Indiana University and Comprehensive Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

Hattiesburg Clinic; 🇺🇸 Hattiesburg, Mississippi, United States

Stony Brook University Hospital; 🇺🇸 Stony Brook, New York, United States

Clinical Research Alliance Inc; 🇺🇸 Westbury, New York, United States

Prohealth Care Inc; 🇺🇸 Waukesha, Wisconsin, United States

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

Pindara Private Hospital; 🇦🇺 Benowa, Queensland, Australia

Epworth Freemasons; 🇦🇺 East Melbourne, Victoria, Australia

Ordensklinikum Linz; 🇦🇹 Linz, Osterreich, Austria

Kepler University Hospital; 🇦🇹 Linz, Upper Austria, Austria

Medical University Vienna; 🇦🇹 Vienna, Austria

Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital; 🇧🇪 Gent, Oost-Vlaanderen, Belgium

Az Delta; 🇧🇪 Roeselare, West Vlaanderen, Belgium

Ziekenhuis Netwerk Antwerpen Stuivenberg; 🇧🇪 Antwerp, Belgium

Centre Hospitalier Universitaire at Universite Catholique de Louvain Namur; 🇧🇪 Yvoir, Belgium

University Hospital Hradec Kralove; 🇨🇿 Hradec Kralove, East Bohemia, Czechia

University Hospital Kralovske Vinohrady; 🇨🇿 Prague, Czechia

Vseobecna Fakultni Nemocnice V Praze; 🇨🇿 Praha, Czechia

Centre Hospitalier Universitaire de Rennes; 🇫🇷 Rennes, Bretagne, France

Centre Hospitalier Regional Universitaire de Tours; 🇫🇷 Tours, Centre Val De Loire, France

Polyclinique Bordeaux Nord Aquitaine; 🇫🇷 Bordeaux Cedex, Gironde, France

Centre Francois Magendie; 🇫🇷 Pessac, Gironde, France

Hopital Victor Dupouy Argenteuil; 🇫🇷 Argenteuil, Ile De France, France

Avicenne Hospital; 🇫🇷 Bobigny, Ile De France, France

Hopital Saint Vincent de Paul; 🇫🇷 Lille, Nord, France

Centre Henri Becquerel; 🇫🇷 Rouen, Normandie, France

Nantes University Hospital; 🇫🇷 Nantes, Pays De La Loire, France

Centre Hospitalier Metropole Savoie; 🇫🇷 Chambery, Savoie, France

Gustave Roussy; 🇫🇷 Villejuif, Val De Marne / Ile De France, France

Centre Hospitalier d'Avignon; 🇫🇷 Avignon, France

Centre Hospitalier Universitaire (CHU) Montpellier; 🇫🇷 Montpellier, France

Hopital Saint Louis; 🇫🇷 Paris, France

Assistance Publique-Hopitaux de Paris (AP-HP); 🇫🇷 Paris, France

Stauferklinikum; 🇩🇪 Mutlangen, Baden-Wuerttemberg, Germany

Robert-Bosch-Krankenhaus; 🇩🇪 Stuttgart, Baden-Wurttemberg, Germany

Clinic Frankfurt (Oder); 🇩🇪 Frankfurt, Hesse, Germany

Stadtisches Krankenhaus Kiel; 🇩🇪 Kiel, Germany

Assuta Ashdod Medical Center; 🇮🇱 Ashdod, Israel

Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

Galilee Medical Center; 🇮🇱 Nahariya, Israel

Rabin Medical Center; 🇮🇱 Petah Tikva, Israel

Chaim Sheba Medical Center; 🇮🇱 Ramat-Gan, Israel

Assuta Medical Centers; 🇮🇱 Tel Aviv, Israel

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori; 🇮🇹 Meldola, Forli Cesena, Italy

S Gerardo Hospital; 🇮🇹 Monza, Monza E Brianza, Italy

Centro Di Riferimento Oncologico (CRO), Aviano, National Cancer Institute; 🇮🇹 Aviano, Province Of Pordenone, Italy

Candiolo Cancer Institute, FPO, IRCCS; 🇮🇹 Candiolo, Torino, Italy

University of Bologna Dipartimento di Medicina Specialistica Diagnostica e Sperimentale; 🇮🇹 Bologna, Italy

Azienda Ospedaliera Spedali Civili di Brescia; 🇮🇹 Brescia, Italy

Ospedale Policlinico San Martino Irccs; 🇮🇹 Genova, Italy

Istituto Europeo di Oncologia; 🇮🇹 Milano, Italy

ASST Grande Ospedale Metropolitano Niguarda - Main Address; 🇮🇹 Milan, Italy

A.O.U. di Modena; 🇮🇹 Modena, Italy

Federico II University; 🇮🇹 Napoli, Italy

AOU Maggiore della Carita; 🇮🇹 Novara, Italy

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Italy

Azienda Ospedaliera di Perugia; 🇮🇹 Perugia, Italy

Ospedale Santa Maria delle Croci; 🇮🇹 Ravenna, Italy

Santa Maria della Misericordia; 🇮🇹 Udine, Italy

St. Vincents Hospital - The Catholic University of Korea; 🇰🇷 Suwon-si, Gyeonggi-do, Korea, Republic of

Jeonbuk National University Hospital; 🇰🇷 Jeonju, Jeollabuk, Korea, Republic of

Gachon University Gil Medical Center; 🇰🇷 Incheon, Namdong-Gu, Korea, Republic of

Inje University Busan Paik Hospital; 🇰🇷 Busan, Korea, Republic of

Pusan National University Hospital; 🇰🇷 Busan, Korea, Republic of

Yeyungnam University Medical Center; 🇰🇷 Daegu, Korea, Republic of

Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Yeouido St. Marys Hospital; 🇰🇷 Seoul, Korea, Republic of

Seoul St Marys Hospital; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Ulsan University Hospital; 🇰🇷 Ulsan, Korea, Republic of

Hospital Sultanah Aminah Jhor Bahru; 🇲🇾 Johor Bahru, Johor, Malaysia

University of Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Negeri / Wilayah Persekutuan, Malaysia

Hospital Queen Elizabeth; 🇲🇾 Kota Kinabalu, Sabah, Malaysia

Hospital Ampang; 🇲🇾 Ampang, Selangor, Malaysia

Subang Jaya Medical Center; 🇲🇾 Subang Jaya, Selangor, Malaysia

Uniwersytecki Szpital Kliniczny; 🇵🇱 Wroclaw, Dolnoslaskie, Poland

Specjalistyczny Szpital im A. Sokolowskiego w Walbrzychu; 🇵🇱 Walbrzych, Lower Silesian, Poland

Pratia MCM Krakow; 🇵🇱 Krakow, Malopolska, Poland

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdansk, Pomorskie, Poland

Pratia Poznan Medical Center; 🇵🇱 Poznan, Wielkopolska, Poland

Aidport; 🇵🇱 Skorzewo, Wielkopolska, Poland

Szpital Uniwersytecki Nr2 Bydgoszcz; 🇵🇱 Bydgoszcz, Poland

Pratia Onkologia Katowice; 🇵🇱 Katowice, Poland

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Mikolaja Kopernika w Lodzi (Copernicus Memorial Hospital); 🇵🇱 Lodz, Poland

Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie, Centrum Innowacyjnych Terapii; 🇵🇱 Lublin, Poland

Narodowy Instytut Onkologii - Clinical Study Location -; 🇵🇱 Warsaw, Poland

University Hospital of Santiago de Compostela; 🇪🇸 Santiago de Compostela, A Coruna, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Son Espases University Hospital; 🇪🇸 Palma, Balearic Islands, Spain

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

Hospital Universitario Quironsalud Madrid; 🇪🇸 Pozuelo de Alarcon, Madrid, Spain

University Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Virgen De Las Nieves De Granada; 🇪🇸 Granada, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Fundacion Jimenez Diaz University Hospital; 🇪🇸 Madrid, Spain

Hospital Universitario12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario HM Sanchinarro, Servicio de Hematologia; 🇪🇸 Madrid, Spain

Hospital Universitario de Salamanca; 🇪🇸 Salamanca, Spain

University Hospital Virgen del Rocio; 🇪🇸 Seville, Spain

Instituto Valenciano de Oncologia; 🇪🇸 Valencia, Spain

University Hospital Doctor Peset; 🇪🇸 Valencia, Spain

Chang Gung Medical Foundation Chia Yi Branch; 🇨🇳 Puzi City, Chiayi County, Taiwan

Changhua Christian Hospital; 🇨🇳 Changhua city, Taiwan

Show Chwan Memorial Hospital; 🇨🇳 Changhua City, Taiwan

Kaohsiung Medical University Hospital; 🇨🇳 Kaohsiung, Taiwan

Taipei Medical University - Shuang Ho Hospital; 🇨🇳 New Taipei City, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan City, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei City, Taiwan

Tri-Service General Hospital; 🇨🇳 Taipei City, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Taipei Municipal Wan Fang Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Memorial Hospital; 🇨🇳 Taoyuan City, Taiwan

Chulalongkorn University; 🇹🇭 Bangkok, Krung Thep Maha Nakhon [Bangko], Thailand

Sriraj Hospital; 🇹🇭 Bangkok, Thailand

Chiang Mai University; 🇹🇭 Chiang Mai, Thailand

Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital; 🇹🇷 Yenimahalle, Ankara, Turkey

Gazi University; 🇹🇷 Ankara, Central Anatolia, Turkey

VM Medical Park Mersin Hospital; 🇹🇷 Mezitli, Mersin, Turkey

Tekirdag Namik Kemal University Hospital; 🇹🇷 Tekirdag, Suleymanpasa, Turkey

Istanbul University, Istanbul Medical Faculty; 🇹🇷 Istanbul, Turkey

Ege University; 🇹🇷 Izmir, Turkey

Dokuz Eylul University; 🇹🇷 Izmir, Turkey

Sakarya University Medical Faculty; 🇹🇷 Sakarya, Turkey

Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi; 🇹🇷 Samsun, Turkey

Zonguldak Bulent Ecevit Univesity; 🇹🇷 Zonguldak, Turkey

Royal Cornwall Hospital NHS Trust; 🇬🇧 Truro, Cornwall, United Kingdom

Derriford Hospital and the Royal Eye Infirmary; 🇬🇧 Plymouth, Devon, United Kingdom

University Hospitals Dorset; 🇬🇧 Bournemouth, Dorset, United Kingdom

Barking, Havering and Redbridge University Hospitals NHS Trust; 🇬🇧 Romford, Essex, United Kingdom

Salisbury Foundation Trust; 🇬🇧 Salisbury, Hampshire, United Kingdom

The Hillingdon Hospital; 🇬🇧 Uxbridge, Middlesex, United Kingdom

James Paget University Hospitals Nhs Foundation Trust; 🇬🇧 Great Yarmouth, United Kingdom

South Warwickshire NHS Foundation Trust; 🇬🇧 Warwick, United Kingdom