A Phase 3, Open label, Randomized Study Comparing the Efficacy and Safety of Odronextamab (REGN1979), an anti-CD20 × anti-CD3 bispecific antibody, in Combination with CHOP (Odro-CHOP) versus Rituximab in Combination with CHOP (R-CHOP) in Previously Untreated Participants with Diffuse Large B-cell Lymphoma (DLBCL) (OLYMPIA-3)

Regeneron Pharmaceuticals Inc.98 sites in 5 countries419 target enrollmentSeptember 8, 2023

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Not specified
Sponsor: Regeneron Pharmaceuticals Inc.
Enrollment: 419
Locations: 98
Primary Endpoint: Part 1: Incidence of dose limiting toxicities (DLTs)
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

Study Objectives- Part 1 (Safety Run-in): To assess the safety, tolerability and dose limiting toxicities (DLTs) of odronextamab in combination with CHOP (Odro-CHOP) in participants previously untreated for Diffuse Large B-Cell Lymphoma (DLBCL) with high-risk features or participants with relapsed or refractory DLBCL (Part 1A), and to determine the dose of odronextamab to combine with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in Part 2.

Study Objectives – Part 2: To compare the efficacy of Odro-CHOP with that of rituximab-CHOP (R-CHOP) in participants with previously untreated DLBCL with an (International Prognostic Index) IPI score ≥3, and subsequently in all participants with an IPI score ≥2.

Registry

euclinicaltrials.eu

Start Date

September 8, 2023

End Date

TBD

Last Updated

last year

Investigators

Sponsor

Regeneron Pharmaceuticals Inc.

Responsible Party

Principal Investigator

Head EU Regulatory Affairs

Scientific

Regeneron Pharmaceuticals Inc.

Eligibility Criteria

Inclusion Criteria

•Previously untreated participants for lymphoma with documented cluster of differentiation 20+ (CD20+) DLBCL, as described in the protocol or R/R DLBCL for whom next available standard of care therapy is not available or deemed ineligible according to investigator (Part 1A only)
•Measurable disease with at least one nodal lesion or at least one extranodal lesion, as described in the protocol
•Eastern Cooperative Oncology Group (ECOG) performance status ≤2
•Life expectancy ≥ 12 months
•International Prognostic Index (IPI) of 3 to 5 (part 1 only) and ≥2 (part 2) for untreated DLBCL only
•Adequate hematologic and organ function, as defined in the protocol
•Note: Other protocol-defined Inclusion criteria apply

Exclusion Criteria

•Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL and history or current relevant CNS pathology
•Another active malignancy, significant active disease or medical condition, as described in the protocol
•Peripheral neuropathy Grade ≥3
•Treatment with any systemic anti-lymphoma therapy , except for participants with R/R DLBCL and participants with DLBCL transformed from an indolent follicular lymphoma after treatment with systemic anti-lymphoma therapy.
•Any other therapy or investigational treatment within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment
•Recent major surgery, prior organ transplantation, or standard radiotherapy, as described in the protocol
•Allergy/hypersensitivity to study drugs, as described in the protocol
•Infections such as any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other), active Coronavirus disease (COVID-19) infection, uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV), Cytomegalovirus (CMV) infection, as described in the protocol.
•Note: Other protocol-defined Exclusion criteria apply

Outcomes

Primary Outcomes

Part 1: Incidence of dose limiting toxicities (DLTs)

Part 1: Incidence of treatment emergent adverse events (TEAEs)

Part 1: Severity of TEAEs

Part 2: Progression free survival (PFS), assessed by independent central review (ICR)

Secondary Outcomes

Part 1 & 2: Best Overall response (BOR) as assessed by local investigators
Part 1 & 2: CR as assessed by local investigators
Part 1 & 2: Duration of response (DOR) as assessed by local investigators
Part 1 & 2: Odronextamab concentrations in serum when administered with CHOP
Part 1 & 2: Incidence of anti-drug antibodies (ADA) to odronextamab over the study duration
Part 1 & 2: Titer of ADA to odronextamab over the study duration
Part 1 & 2: Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration
Part 2: Event-free survival (EFS) assessed by ICR
Part 2: Complete response (CR) assessed by ICR
Part 2: Overall survival (OS)
Part 2: PFS assessed by local investigator review
Part 2: EFS assessed by local investigator review
Part 2: BOR assessed by ICR
Part 2: DOR assessed by ICR
Part 2: Incidence of TEAEs
Part 2: Severity of TEAEs
Part 2: Measurable Residual Disease (MRD) status
Part 2: Duration of MRD-negativity
Part 2: Change in physical functioning as measured by EORTC QLQ C30
Part 2: Change in patient reported outcomes, as measured by EORTC QLQ-C30
Part 2: Change in patient reported outcomes, as measured by FACT-LymS
Part 2: Change in patient reported outcomes, as measured by PGIS
Part 2: Change in patient reported outcomes, as measured by PGIC
Part 2: Change in patient reported outcomes, as measured by EQ-5D-5L
Part 2: Change in score of the FACT-G GP5 item