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

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 in Relapsed/Refractory Participants With Follicular Lymphoma and Marginal Zone Lymphoma (OLYMPIA-5)

Overview

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

Interventions

• Drug Odronextamab
  Administered per the protocol
• Drug Lenalidomide
  Administered per the protocol
• Drug Rituximab
  Administered per the protocol

Primary outcome measures

• Incidence of Dose Limiting Toxicities (DLTs) for odronextamab in combination with lenalidomide [Time frame: Up to 35 days]
• Incidence of Treatment Emergent Adverse Events (TEAEs) for odronextamab in combination with lenalidomide [Time frame: Up to 2 years]
• Severity of TEAEs for odronextamab in combination with lenalidomide [Time frame: 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 [Time frame: Up to 5 years]

Secondary outcome measures (12)

• Odronextamab concentrations in serum [Time frame: Up to 30 months]
• Incidence of Anti-drug Antibodies (ADA) to odronextamab [Time frame: Up to 30 months]
• Magnitude of ADAs to odronextamab [Time frame: Up to 30 months]
• Best Overall Response (BOR) as assessed by investigator review [Time frame: Up to 30 months]
• Duration of Response (DOR) as assessed by investigator review [Time frame: Up to 5 years]
• PFS as assessed by investigator review [Time frame: Up to 5 years]
• Complete Response (CR) as assessed by ICR [Time frame: Up to 30 months]
• BOR as assessed by ICR [Time frame: Up to 30 months]
• Overall Survival (OS) [Time frame: Up to 5 years]
• Event Free Survival (EFS) as assessed by ICR [Time frame: Up to 5 years]
• EFS as assessed by local investigator review [Time frame: Up to 5 years]
• DOR as assessed by ICR [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• 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.
• 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.
• Have measurable disease on cross sectional imaging documented by diagnostic Computed Tomography \[CT\], or Magnetic Resonance Imaging \[MRI\] imaging, as described in the protocol.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Adequate hematologic and organ function, as described in the protocol.
• All study participants must:

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

Exclusion criteria

• 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.
• 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.
• History of or current relevant CNS pathology, as described in the protocol.
• 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.
• 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.
• Allergy/hypersensitivity to study drugs or excipients. as described in the protocol.
• Active infection as defined in the protocol.

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 18 centers

• Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori — Meldola
• Ospedale Policlinico San Martino IRCCS — Genoa
• S Gerardo Hospital — Monza
• A.O.U. Citta della Salute e della Scienza di Torino — Turin
• Centro Di Riferimento Oncologico (CRO), Aviano, National Cancer Institute — Aviano
• Candiolo Cancer Institute, FPO, IRCCS — Candiolo
• University of Bologna Dipartimento di Medicina Specialistica Diagnostica e Sperimentale — Bologna
• Azienda Ospedaliera Spedali Civili di Brescia — Brescia
• … and 10 more centers

Spain · 18 centers

Center list to be confirmed — check the primary protocol.

France · 17 centers

• Institut Paoli-Calmettes — Marseille
• CHU de Rennes — Rennes
• Centre Hospitalier Regional Universitaire de Tours — Tours
• Polyclinique Bordeaux Nord Aquitaine — Bordeaux
• Centre Francois Magendie — Pessac
• Hopital Saint Vincent-de-Paul — Lille
• Centre Henri Becquerel — Rouen
• Nantes University Hospital — Nantes
• … and 9 more centers

South Korea · 13 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 12 centers

Center list to be confirmed — check the primary protocol.

Poland · 11 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 11 centers

Center list to be confirmed — check the primary protocol.

Brazil · 10 centers

• Hospital Sao Rafael — Salvador
• Hospital Sirio Libanes Brasilia — Brasília
• Uopeccan Hospital do Cancer de Cascavel — Cascavel
• Hospital Erasto Gaertner — Curitiba
• Hospital de Clinicas de Porto Alegre — Porto Alegre
• Centro Gaucho Integrado — Porto Alegre
• Amaral Carvalho Hospital — Jaú
• Instituto Nacional de Cancer Jose Alencar Gomes da Silva — Rio de Janeiro
• … and 2 more centers

Germany · 9 centers

• Stauferklinikum — Mutlangen
• Robert-Bosch-Krankenhaus — Stuttgart
• LMU Klinikum — Munich
• TUM Fakultat fur Medizin - Klinikum Rechts der Isar — Munich
• Clinic Frankfurt (Oder) — Frankfurt am Main
• Universitatsmedizin der Johannes-Gutenberg Universitat Mainz — Mainz
• University Hospital Halle Saale — Halle
• Stadtisches Krankenhaus Kiel — Kiel
• … and 1 more center

United Kingdom · 9 centers

Center list to be confirmed — check the primary protocol.

United States · 8 centers

• David Geffen School of Medicine at UCLA — Los Angeles
• Boca Raton Clinical Research (BRCR) Global — Plantation
• Indiana University and Comprehensive Cancer Center — Indianapolis
• Hattiesburg Clinic — Hattiesburg
• Dartmouth Cancer Center — Lebanon
• Stony Brook University Hospital — Stony Brook
• Clinical Research Alliance Inc — Westbury
• Prohealth Care Inc — Waukesha

Israel · 7 centers

• Assuta Ashdod Medical Center — Ashdod
• Hadassah Medical Center — Jerusalem
• Galilee Medical Center — Nahariya
• Rabin Medical Center — Petah Tikva
• Chaim Sheba Medical Center — Ramat Gan
• The Tel Aviv Sourasky Medical Center — Tel Aviv
• Assuta Medical Centers — Tel Aviv

Australia · 5 centers

• Liverpool Hospital — Liverpool
• Calvary Mater Newcastle — Waratah
• Pindara Private Hospital — Benowa
• Royal Hobart Hospital — Hobart
• Epworth Freemasons — East Melbourne

Belgium · 5 centers

• Centre Hospitalier Universitaire at Universite Catholique de Louvain Namur — Yvoir
• Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital — Ghent
• Algemeen Ziekenhuis AZ Delta — Roeselare
• Ziekenhuis Netwerk Antwerpen Stuivenberg — Antwerp
• Institut Jules Bordet — Brussels

Malaysia · 5 centers

Center list to be confirmed — check the primary protocol.

Austria · 4 centers

• Ordensklinikum Linz — Linz
• Kepler University Hospital — Linz
• Medical University Vienna — Vienna
• Klinikum Wels-Grieskirchen — Wels

Czechia · 4 centers

• University Hospital Hradec Kralove — Hradec Králové
• Fakultni Nemocnice Brno — Brno
• University Hospital Kralovske Vinohrady — Prague
• Vseobecna Fakultni Nemocnice V Praze — Prague

Thailand · 3 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06149286 · R1979-ONC-22102 · 2022-503092-28-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗