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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 216
- Locations
- 141
- Primary Endpoint
- Event-free survival (EFS) as assessed by independent central review (ICR)
Study Overview
Brief Summary
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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
- •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])
- •Intent to proceed to autologous stem cell transplant (ASCT), as described in the protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Adequate hematologic and organ function.
Exclusion Criteria
- •Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL, as described in the protocol
- •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, 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
- •Wash-out period from prior anti-lymphoma treatments and infections, as described in the protocol
- •Allergy/hypersensitivity to study drug, or excipients.
- •NOTE: Other protocol defined inclusion / exclusion criteria apply
Arms & Interventions
Odronextamab
Participants will receive odronextamab monotherapy.
Intervention: Odronextamab (Drug)
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).
Intervention: Etoposide (Drug)
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).
Intervention: Carboplatin (Drug)
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).
Intervention: Cytarabine (Drug)
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).
Intervention: Cisplatin (Drug)
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).
Intervention: Gemcitabine (Drug)
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).
Intervention: Ifosfamide (Drug)
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).
Intervention: Rituximab (Drug)
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).
Intervention: Dexamethasone (Drug)
Outcomes
Primary Outcomes
Event-free survival (EFS) as assessed by independent central review (ICR)
Time Frame: Assessed up to 3 years
Secondary Outcomes
- Progression free survival (PFS) as assessed by ICR(Assessed up to 3 years)
- Best overall response (BOR) as assessed by ICR(Assessed up to 6 months)
- Overall survival (OS)(Assessed up to 3 years)
- Overall change 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)(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 ICR(Assessed up to 6 months)
- CR as assessed by local investigator(Assessed up to 6 months)
- Duration of response (DOR) assessed by ICR(Assessed up to 3 years)
- DOR assessed by local investigator(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 over the study duration(Assessed up to 6 months)
- Titers of ADAs to odronextamab over the study duration(Assessed up to 6 months)
- Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration(Assessed up to 6 months)
- Measurable residual disease (MRD) status(Assessed up to 6 months)
- Overall change in patient-reported outcomes (PROs), as measured by scores of the EORTCQLQ- C30(Assessed up to 3 years)
- Overall change in PROs, as measured by scores of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-LymS)(Assessed up to 3 years)
- Overall change in PROs, as measured by scores of the EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)(Assessed up to 3 years)
- Overall change in score of the Global Population item 5 (GP5) of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire(Assessed up to 3 years)
- Overall survival (OS)(Assessed up to 3 years)
- Overall change 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)(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 ICR(Assessed up to 6 months)
- CR as assessed by local investigator(Assessed up to 6 months)
- Duration of response (DOR) assessed by ICR(Assessed up to 3 years)
- DOR assessed by local investigator(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 over the study duration(Assessed up to 6 months)
- Titers of ADAs to odronextamab over the study duration(Assessed up to 6 months)
- Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration(Assessed up to 6 months)
- Measurable residual disease (MRD) status(Assessed up to 6 months)
- Overall change in patient-reported outcomes (PROs), as measured by scores of the EORTCQLQ- C30(Assessed up to 3 years)
- Overall change in PROs, as measured by scores of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-LymS)(Assessed up to 3 years)
- Overall change in PROs, as measured by scores of the EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)(Assessed up to 3 years)
- Overall change in score of the Global Population item 5 (GP5) of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire(Assessed up to 3 years)