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 (OLYMPIA-4)

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)

The 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 effective the study drug is compared to standard of care (SOC) therapy.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug versus SOC
• How much study drug is in your blood at different times
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
• Comparing the impact from the study drug versus SOC on your quality-of-life and ability to complete routine daily activities

Study Overview

• Status: Recruiting
• Conditions: B-Cell Non-Hodgkin Lymphoma (B-NHL)
• Intervention / Treatment: Drug: Odronextamab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide; Drug: Rituximab; Drug: Dexamethasone; Drug: Cisplatin; Drug: Cytarabine; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, VIC 3084
      • Recruiting
      • Austin Cancer Clinical Trails
• Italy
  • Novara, Italy, 28100
    • Recruiting
    • AOU Maggiore della Carità
• Spain
  • Granada, Spain, 18014
    • Recruiting
    • Hospital Universitario Virgen de las Nieves
  • Madrid, Spain, 28031
    • Recruiting
    • Hospital Universitario Infanta Leonor
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28223
    • Recruiting
    • Hospital Universitario Quironsalud Madrid
  • Madrid, Spain, 28027
    • Recruiting
    • Clinica Universidad de Navarra - Sede Madrid
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46017
    • Recruiting
    • Hospital Universitario Doctor Peset
  • Barcelona
    • Terrassa, Barcelona, Spain, 08021
      • Recruiting
      • Hospital Mutua De Terrassa
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
  • Palma De Mallorca
    • Palma, Palma De Mallorca, Spain, 7120
      • Recruiting
      • Hospital Son Espases
• Taiwan
  • Guishan District
    • Taoyuan, Guishan District, Taiwan, 333
      • Recruiting
      • Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Siriraj Institute
  • Chiang Mai, Thailand, 50200
    • Recruiting
    • Chiang Mai University
• Turkey
  • Ankara, Turkey, 06100
    • Recruiting
    • Ankara Research Hospital
  • Sakarya
    • Serdivan, Sakarya, Turkey, 54290
      • Recruiting
      • Sakarya University Training and Research Hospital
  • Suleymanpasa
    • Tekirdag, Suleymanpasa, Turkey, 59100
      • Recruiting
      • Namik Kemal Universitesi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

   Treatment at frontline should have included anti-cluster of differentiation 20 (anti-CD20) antibody and anthracycline-containing regimen.

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).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
6. Adequate hematologic and organ function.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Odronextamab; Participants will receive odronextamab monotherapy.	Drug: Odronextamab; Administered by intravenous (IV) infusion; Other Names: R1979
Active Comparator: Standard Of Care; Participants will receive salvage therapy (ifosfamide, carboplatin, etoposide ± rituximab [ICE ± R], or dexamethasone, cisplatin, cytarabine ± rituximab [DHAP ± R], or gemcitabine, dexamethasone, cisplatin ± rituximab [GDP ± R]) and continue with autologous stem cell transplant (ASCT) following a complete response (CR)/partial response (PR).	Drug: Ifosfamide; Administered by IV infusion, as part of the ICE ± R salvage therapy; Other Names: Ifex; Drug: Carboplatin; Administered by IV infusion, as part of the ICE ± R salvage therapy; Other Names: Paraplatin; Drug: Etoposide; Administered by IV infusion, as part of the ICE ± R salvage therapy; Other Names: Etopophos; Drug: Rituximab; Administered by IV infusion, as part of the ICE ± R, or DHAP ± R, or GDP ± R salvage therapy.; Other Names: Rituxan; Drug: Dexamethasone; Administered by IV, or orally (PO) as part of the DHAP ± R, or GDP ± R salvage therapy.; Other Names: Decadron; Drug: Cisplatin; Administered by IV infusion, as part of the DHAP ± R or GDP +/-R salvage therapy.; Other Names: Platinol; Drug: Cytarabine; Administered by IV infusion, as part of the DHAP ± R salvage therapy.; Other Names: Cytosar-U; Drug: Gemcitabine; Administered by IV infusion, as part of the GDP ± R salvage therapy.; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Event-free survival (EFS) as assessed by independent central review	Assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) as assessed by independent central review		Assessed up to 3 years
Best overall response (BOR) as assessed by independent central review		Assessed up to 6 months
Overall change from baseline in physical functioning as measured by scores of the physical function scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30)	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.	Assessed up to 3 years
EFS as assessed by local investigator		Assessed up to 3 years
PFS as assessed by local investigator		Assessed up to 3 years
BOR as assessed by local investigator		Assessed up to 6 months
Complete response (CR) as assessed by independent central review		Assessed up to 6 months
CR as assessed by local investigator		Assessed up to 6 months
Duration of response (DOR) assessed by independent central review		Assessed up to 3 years
DOR assessed by local investigator		Assessed up to 3 years
Overall survival (OS)		Assessed up to 3 years
Incidence of treatment-emergent adverse events (TEAEs)		Assessed up to 1 year
Severity of TEAEs		Assessed up to 1 year
Odronextamab concentrations in serum		Assessed up to 6 months
Incidence of anti-drug antibodies (ADAs) to odronextamab		Assessed up to 6 months
Titers of ADAs to odronextamab		Assessed up to 6 months
Incidence of neutralizing antibodies (NAb) to odronextamab		Assessed up to 6 months
Measurable residual disease (MRD) status		Assessed up to 6 months
Duration of MRD-negativity, as determined by circulating tumor DNA (ctDNA)		Assessed up to 3 years
Overall change from baseline in patient-reported outcomes, as measured by scores of the EORTCQLQ- C30	The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a 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.	Assessed up to 3 years
Overall change from baseline in patient-reported outcomes, as measured by scores of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-LymS)	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.	Assessed up to 3 years
Overall change from baseline in patient-reported outcomes, as measured by scores of the EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)	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".	Assessed up to 3 years
Overall change from first assessment to end of treatment in score of the Global Population item 5 (GP5) of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire	A single item Global Population item 5 (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).	Assessed up to 3 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): July 6, 2027
• Study Completion (Estimated): July 6, 2027

Study Registration Dates

• First Submitted: December 29, 2023
• First Submitted That Met QC Criteria: January 18, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Odronextamab; Anti-CD20 × anti-CD3 bispecific antibody; Non-Hodgkin lymphomas (NHLs); B-Cell Non-Hodgkin Lymphoma (B-NHL); Aggressive NHL; Relapsed/Refractory NHL
• Additional Relevant MeSH Terms: Behavioral Symptoms; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Aberrant Motor Behavior in Dementia; Aggression; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Dexamethasone; Carboplatin; Etoposide; Ifosfamide; Rituximab; Cytarabine; Gemcitabine
• Other Study ID Numbers: R1979-HM-2299; 2022-502783-21-00 (Other Identifier: EUCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
• IPD Sharing Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Access Criteria: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes