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

Studio Clinico

Patologia: Linfomi

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Seconda linea

Criteri di inclusione: 

- 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.
- Have refractory disease or relapsed after at least one 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:
   a. Have an understanding that lenalidomide could have a potential teratogenic risk.
   b. Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of lenalidomide.     c. Agree not to share study medication with another person.
   d. Agree to be counseled about pregnancy precautions and risk of fetal exposure associated with lenalidomide.

Criteri di esclusione: 

- Primary central nervous system (CNS) lymphoma or known involvement (either current or prior history of CNS involvement) by non-primary CNS Non-Hodgkin lymphoma (NHL), as described in the protocol.
- 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.
- History of or current relevant CNS pathology, as described in the protocol.
- 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.
- 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.

Trattamento sperimentale: 

Odronextamab + Lenalidomide

Trattamento di controllo: 

Rituximab + Lenalidomide

Obiettivi primari dello studio: 

Part 1 (Safety Run-In) Assess the safety, tolerability, and dose-limiting toxicities (DLTs) of odronextamab in combination with lenalidomide in participants with relapsed/refractory (R/R) indolent lymphoma (FL and MZL).

Part 2 (Randomized Phase) To compare the efficacy of odronextamab in combination with lenalidomide versus rituximab in combination with lenalidomide (R2) in participants with R/R FL and subsequently in participants with indolent lymphoma (combined R/R FL and marginal zone lymphoma (MZL)) as measured by progression-free survival (PFS) per independent central review.

Obiettivi secondari dello studio: 

- Part 1: To characterize the pharmacokinetics (PK) of odronextamab in participants with R/R indolent lymphoma.
- Part 1: To assess the immunogenicity of odronextamab
- Part 1:To evaluate the preliminary anti-tumor activity of odronextamab in participants with R/R indolent lymphoma

 Part 2: To compare efficacy of odronextamab in combination with lenalidomide versus R2 as measured per independent central review by the following endpoints: Complete response (CR), Best overall response (BOR), Overall survival (OS)
- Part 2: To assess additional measures of efficacy of odronextamab in combination with lenalidomide versus R2
- Part 2: To evaluate safety and tolerability of odronextamab in combination with lenalidomide versus R2 - from secondary objectives
- Part 2: To evaluate the PK of odronextamab
- Part 2: To assess the immunogenicity of odronextamab.
- Part 2: To evaluate the impact of odronextamab in combination with lenalidomide versus R2 on patient-reported outcomes including health-related quality-of-life, functioning symptoms and general health status.
- Part 2: To evaluate patient reported overall impact of treatment toxicity for odronextamab in combination with lenalidomide versus R2.

Studi collaterali: 

Raccolta biomarcatori (ctDNA, immunofenotipo, PK, ADA).

Data di inizio dell'arruolamento: 20.08.2024

Data di fine dell'arruolamento: 25.04.2029

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2022-503092-28-00

Data di inserimento: 27.03.2026

Promotore

Regeneron Pharmaceuticals, Inc.

Email: clinicaltrials@regeneron.com

CRO

ICON

Principal Investigator ITALIA

Riferimento: Dr. - -

Telefono: 00000

Email: na@na.it

Localita: na