Clinical trial NCT06149286: 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
Official title: 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 Therapy in Relapsed/Refractory Participants With Follicular Lymphoma and Marginal Zone Lymphoma (OLYMPIA-5)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Relapsed/Refractory Follicular Lymphoma
Marginal Zone Lymphoma (MZL)
Keywords: Relapsed/Refractory Follicular Lymphoma
Marginal Zone Lymphoma
Non-Hodgkin lymphomas
Indolent lymphomas
Odronextamab
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-11-28
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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 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

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with lenalidomide
timeFrame: Up to 35 days
measure: Incidence of treatment emergent adverse events (TEAEs) for odronextamab in combination with lenalidomide
timeFrame: Up to 2 years
measure: Severity of TEAEs for odronextamab in combination with lenalidomide
timeFrame: Up to 2 years
measure: Progression-free survival (PFS) as assessed by independent central review (ICR) in participants with R/R FL and participants with indolent lymphoma
timeFrame: Up to 5 years
Secondary outcomes:
measure: Odronextamab concentrations in serum
timeFrame: Up to 30 months
measure: Incidence of anti-drug antibodies (ADA) to odronextamab over the study duration
timeFrame: Up to 30 months
measure: Titer of ADAs to odronextamab over the study duration
timeFrame: Up to 30 months
measure: Incidence of neutralizing antibodies (NAbs) to odronextamab over the study duration
timeFrame: Up to 30 months
measure: Best overall response (BOR) as assessed by investigator review
timeFrame: Up to 30 months
measure: Duration of response (DOR) as assessed by investigator review
timeFrame: Up to 5 years
measure: PFS as assessed by investigator review
timeFrame: Up to 5 years
measure: Complete response (CR) as assessed by ICR
timeFrame: Up to 30 months
measure: BOR as assessed by ICR
timeFrame: Up to 30 months
measure: Overall survival (OS)
timeFrame: Up to 5 years
measure: Event free survival (EFS) as assessed by ICR
timeFrame: Up to 5 years
measure: EFS as assessed by local investigator review
timeFrame: Up to 5 years
measure: DOR as assessed by ICR
timeFrame: Up to 5 years
measure: Time to next anti-lymphoma treatment (TTNT)
timeFrame: Up to 5 years
measure: Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2
timeFrame: Up to 2 years
measure: Severity of TEAEs for odronextamab in combination with lenalidomide versus R2
timeFrame: Up to 2 years
measure: 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)
timeFrame: Up to 5 years
measure: Overall change in PROs as measured by scores of Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)
timeFrame: Up to 5 years
measure: Overall change in PROs as measured by scores of Patient Global Impression on Severity (PGIS)
timeFrame: Up to 5 years
measure: Overall change in PROs as measured by scores of Patient Global Impression on Change (PGIC)
timeFrame: Up to 5 years
measure: Overall change in PROs as measured by scores of EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)
timeFrame: Up to 5 years
measure: Overall change in score of the global population item 5 (GP5) items of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Plantation
country: United States
facility: Boca Raton Clinical Research (BRCR) Global
state: Florida
city: Indianapolis
country: United States
facility: Indiana University and Comprehensive Cancer Center
state: Indiana
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance Inc
state: New York
city: Waukesha
country: United States
facility: Prohealth Care Inc
state: Wisconsin
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: East Melbourne
country: Australia
facility: Epworth Freemasons
state: Victoria
city: Linz
country: Austria
facility: Ordensklinikum Linz
state: Osterreich
city: Linz
country: Austria
facility: Kepler University Hospital
state: Upper Austria
city: Vienna
country: Austria
facility: Medical University Vienna
city: Wels
country: Austria
facility: Klinikum Wels Grieskirchen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital
state: Oost-Vlaanderen
city: Roeselare
country: Belgium
facility: Az Delta
state: West Vlaanderen
city: Antwerp
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Stuivenberg
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Yvoir
country: Belgium
facility: Centre Hospitalier Universitaire at Universite Catholique de Louvain Namur
city: Hradec Kralove
country: Czechia
facility: University Hospital Hradec Kralove
state: East Bohemia
city: Prague
country: Czechia
facility: University Hospital Kralovske Vinohrady
city: Praha
country: Czechia
facility: Vseobecna Fakultni Nemocnice V Praze
city: Marseille
country: France
facility: Institut Paoli-Calmettes
state: Bouches Du Rhone
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes
state: Bretagne
city: Tours
country: France
facility: Centre Hospitalier Regional Universitaire de Tours
state: Centre Val De Loire
city: Bordeaux Cedex
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
state: Gironde
city: Pessac
country: France
facility: Centre Francois Magendie
state: Gironde
city: Argenteuil
country: France
facility: Hopital Victor Dupouy Argenteuil
state: Ile De France
city: Bobigny
country: France
facility: Avicenne Hospital
state: Ile De France
city: Lille
country: France
facility: Hopital Saint Vincent de Paul
state: Nord
city: Rouen
country: France
facility: Centre Henri Becquerel
state: Normandie
city: Nantes
country: France
facility: Nantes University Hospital
state: Pays De La Loire
city: Chambery
country: France
facility: Centre Hospitalier Metropole Savoie
state: Savoie
city: Villejuif
country: France
facility: Gustave Roussy
state: Val De Marne / Ile De France
city: Avignon
country: France
facility: Centre Hospitalier d'Avignon
city: Montpellier
country: France
facility: Centre Hospitalier Universitaire (CHU) Montpellier
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Assistance Publique-Hopitaux de Paris (AP-HP)
city: Mutlangen
country: Germany
facility: Stauferklinikum
state: Baden-Wuerttemberg
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
state: Baden-Wurttemberg
city: Frankfurt
country: Germany
facility: Clinic Frankfurt (Oder)
state: Hesse
city: Kiel
country: Germany
facility: Stadtisches Krankenhaus Kiel
city: Ashdod
country: Israel
facility: Assuta Ashdod Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Assuta Medical Centers
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
state: Forli Cesena
city: Monza
country: Italy
facility: S Gerardo Hospital
state: Monza E Brianza
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico (CRO), Aviano, National Cancer Institute
state: Province Of Pordenone
city: Candiolo
country: Italy
facility: Candiolo Cancer Institute, FPO, IRCCS
state: Torino
city: Bologna
country: Italy
facility: University of Bologna Dipartimento di Medicina Specialistica Diagnostica e Sperimentale
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Genova
country: Italy
facility: Ospedale Policlinico San Martino IRCCS
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - Main Address
city: Modena
country: Italy
facility: A.O.U. di Modena
city: Napoli
country: Italy
facility: Federico II University
city: Novara
country: Italy
facility: AOU Maggiore della Carita
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Udine
country: Italy
facility: Santa Maria della Misericordia
city: Suwon-si
country: Korea, Republic of
facility: St. Vincents Hospital - The Catholic University of Korea
state: Gyeonggi-do
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
state: Jeollabuk
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Namdong-Gu
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeyungnam University Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yeouido St. Marys Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St Marys Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah Jhor Bahru
state: Johor
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
state: Negeri / Wilayah Persekutuan
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth
state: Sabah
city: Ampang
country: Malaysia
facility: Hospital Ampang
state: Selangor
city: Subang Jaya
country: Malaysia
facility: Subang Jaya Medical Center
state: Selangor
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny
state: Dolnoslaskie
city: Walbrzych
country: Poland
facility: Specjalistyczny Szpital im A. Sokolowskiego w Walbrzychu
state: Lower Silesian
city: Krakow
country: Poland
facility: Pratia MCM Krakow
state: Malopolska
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Pomorskie
city: Poznan
country: Poland
facility: Pratia Poznan Medical Center
state: Wielkopolska
city: Skorzewo
country: Poland
facility: Aidport
state: Wielkopolska
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr2 Bydgoszcz
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Mikolaja Kopernika w Lodzi (Copernicus Memorial Hospital)
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie, Centrum Innowacyjnych Terapii
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii - Clinical Study Location -
city: Santiago de Compostela
country: Spain
facility: University Hospital of Santiago de Compostela
state: A Coruna
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Palma
country: Spain
facility: Son Espases University Hospital
state: Balearic Islands
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Granada
country: Spain
facility: Hospital Virgen De Las Nieves De Granada
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro, Servicio de Hematologia
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Seville
country: Spain
facility: University Hospital Virgen del Rocio
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: University Hospital Doctor Peset
city: Puzi City
country: Taiwan
facility: Chang Gung Medical Foundation Chia Yi Branch
state: Chiayi County
city: Changhua city
country: Taiwan
facility: Changhua Christian Hospital
city: Changhua City
country: Taiwan
facility: Show Chwan Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital
city: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Municipal Wan Fang Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn University
state: Krung Thep Maha Nakhon [Bangko]
city: Bangkok
country: Thailand
facility: Sriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
city: Yenimahalle
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
state: Ankara
city: Ankara
country: Turkey
facility: Gazi University
state: Central Anatolia
city: Mezitli
country: Turkey
facility: VM Medical Park Mersin Hospital
state: Mersin
city: Tekirdag
country: Turkey
facility: Tekirdag Namik Kemal University Hospital
state: Suleymanpasa
city: Istanbul
country: Turkey
facility: Istanbul University, Istanbul Medical Faculty
city: Izmir
country: Turkey
facility: Ege University
city: Izmir
country: Turkey
facility: Dokuz Eylul University
city: Sakarya
country: Turkey
facility: Sakarya University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
city: Zonguldak
country: Turkey
facility: Zonguldak Bulent Ecevit Univesity
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital NHS Trust
state: Cornwall
city: Plymouth
country: United Kingdom
facility: Derriford Hospital and the Royal Eye Infirmary
state: Devon
city: Bournemouth
country: United Kingdom
facility: University Hospitals Dorset
state: Dorset
city: Romford
country: United Kingdom
facility: Barking, Havering and Redbridge University Hospitals NHS Trust
state: Essex
city: Salisbury
country: United Kingdom
facility: Salisbury Foundation Trust
state: Hampshire
city: Uxbridge
country: United Kingdom
facility: The Hillingdon Hospital
state: Middlesex
city: Great Yarmouth
country: United Kingdom
facility: James Paget University Hospitals Nhs Foundation Trust
city: Warwick
country: United Kingdom
facility: South Warwickshire NHS Foundation Trust
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: