A Trial to Learn How Effective and Safe Odronextamab is Compared to Standard of Care for Adult Participants With Previously Treated Aggressive B-cell Non-Hodgkin Lymphoma

A Phase 3, Randomized, Open Label Study Evaluating the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 x Anti-CD3 Bispecific Antibody, Versus Standard of Care Therapy in Participants With Relapsed/Refractory Aggressive B-cell Non-Hodgkin Lymphoma (OLYMPIA-4)

A Trial to Learn How Effective and Safe Odronextamab is Compared to Standard of Care for Adult Participants With Previously Treated Aggressive B-cell Non-Hodgkin Lymphoma (NCT06230224) is a Phase 3 interventional studying B-Cell Non-Hodgkin Lymphoma (B-NHL), sponsored by Regeneron Pharmaceuticals. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on patients with previously treated aggressive B-cell non-Hodgkin lymphoma whose cancer has stopped responding to treatment (also known as 'refractory') or has returned (also known as 'relapsed'). The aim of the study is to see how safe, tolerable and effective the study drug is when given alone. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug versus Standard of Care (SOC) * 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) * Comparing the impact from the study drug versus SOC on quality-of-life and ability to complete routine daily activities

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For B-Cell Non-Hodgkin Lymphoma (B-NHL), Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 216 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused B-Cell Non-Hodgkin Lymphoma (B-NHL) subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Key Who May Qualify: 1. Histologically proven aggressive B-NHL, as described in the protocol. Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed 2. Have primary refractory or relapse 12 months or less (≤) from initiation of frontline therapy Only patients who received 1 prior line of therapy containing an anti-Cluster of Differentiation 20 (CD20) antibody and anthracycline are allowed for enrollment 3. Have measurable disease with at least one nodal lesion with longer diameter (LDi) greater than 1.5 cm or at least one extranodal lesion with LDi greater than 1.0 cm, documented by diagnostic imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) 4. Intent to proceed to autologous stem cell transplant (ASCT), as described in the protocol 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 6. Adequate hematologic and organ function. Key Who Should NOT Join This Trial: 1. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL, as described in the protocol 2. History of or current relevant CNS pathology, as described in the protocol 3. 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, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated 4. 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 5. Wash-out period from prior anti-lymphoma treatments and infections, as described in the protocol 6. Allergy/hypersensitivity to study drug, or excipients. NOTE: Other protocol defined inclusion / exclusion criteria apply Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Key Inclusion Criteria: 1. Histologically proven aggressive B-NHL, as described in the protocol. Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed 2. Have primary refractory or relapse 12 months or less (≤) from initiation of frontline therapy Only patients who received 1 prior line of therapy containing an anti-Cluster of Differentiation 20 (CD20) antibody and anthracycline are allowed for enrollment 3. Have measurable disease with at least one nodal lesion with longer diameter (LDi) greater than 1.5 cm or at least one extranodal lesion with LDi greater than 1.0 cm, documented by diagnostic imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) 4. Intent to proceed to autologous stem cell transplant (ASCT), as described in the protocol 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 6. Adequate hematologic and organ function. Key Exclusion Criteria: 1. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL, as described in the protocol 2. History of or current relevant CNS pathology, as described in the protocol 3. 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, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated 4. 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 5. Wash-out period from prior anti-lymphoma treatments and infections, as described in the protocol 6. Allergy/hypersensitivity to study drug, or excipients. NOTE: Other protocol defined inclusion / exclusion criteria apply

Treatments Being Tested

DRUG

Odronextamab

Administered by intravenous (IV) infusion

DRUG

Ifosfamide

Administered by IV infusion, as part of the ICE ± R salvage therapy

DRUG

Carboplatin

Administered by IV infusion, as part of the ICE ± R salvage therapy

DRUG

Etoposide

Administered by IV infusion, as part of the ICE ± R salvage therapy

DRUG

Rituximab

Administered by IV infusion, as part of the ICE ± R, or DHAP ± R, or GDP ± R salvage therapy.

DRUG

Dexamethasone

Administered by IV, or orally (PO) as part of the DHAP ± R, or GDP ± R salvage therapy.

DRUG

Cisplatin

Administered by IV infusion, as part of the DHAP ± R or GDP +/-R salvage therapy.

DRUG

Cytarabine

Administered by IV infusion, as part of the DHAP ± R salvage therapy.

DRUG

Gemcitabine

Administered by IV infusion, as part of the GDP ± R salvage therapy.

Locations (20)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Hospital Aleman