A Study to Compare How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Against Rituximab Combined With Chemotherapy, in Adult Patients With Previously Untreated Diffuse Large B-cell Lymphoma

Official title

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)

Overview

This study is researching an experimental drug called odronextamab, referred to as study drug, when used in combination with chemotherapy. The study is focused on patients with Diffuse Large B-cell Lymphoma (DLBCL) that have not been treated before (called "previously untreated"). Patients with DLBCL that have come back after treatment (called "relapsed"), or have not responded to treatment (called "refractory"), can also participate in this study. This study will be made up of Part 1A, Part 1B, and Part 2.The aim of Part 1A and Part 1B of the study is to see how safe and tolerable the study drug in combination with chemotherapy is and to determine the dose and schedule of the study drug to be combined with chemotherapy in Part 2 of the study. The aim of Part 2 of the study is to see how effective the combination of the study drug with chemotherapy is in comparison with the combination of rituximab (the comparator drug), and chemotherapy, the current standard of care treatment approved for DLBCL. Standard of care means the usual medication expected and used when receiving treatment for a condition. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug when combined with chemotherapy * 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) * The impact from the study drug on quality of life and ability to complete routine daily activities

Interventions

• Drug Odronextamab
  Odronextamab will be administered by intravenous (IV) infusion
• Drug Rituximab
  Rituximab will be administered IV, or subcutaneously (SC)
• Drug Cyclophosphamide
  Cyclophosphamide will be administered IV as part of chemotherapy
• Drug Doxorubicin
  Doxorubicin will be administered IV as part of chemotherapy
• Drug Vincristine
  Vincristine will be administered IV as part of chemotherapy
• Drug Prednisone/Prednisolone
  Prednisone or prednisolone will be administered orally (PO) as part of chemotherapy

Primary outcome measures

• Incidence of Dose Limiting Toxicities (DLTs) [Time frame: Up to 35 days]
• Incidence of Treatment Emergent Adverse Events (TEAEs) [Time frame: Up to 2 years]
• Severity of TEAEs [Time frame: Up to 2 years]
• Progression Free Survival (PFS), assessed by Independent Central Review (ICR) [Time frame: Up to 5 years]

Secondary outcome measures (12)

• Event-Free Survival (EFS) assessed by ICR [Time frame: Up to 5 years]
• Complete Response (CR) assessed by ICR [Time frame: Up to 22 weeks]
• Overall Survival (OS) [Time frame: Up to 5 years]
• Best Overall Response (BOR) as assessed by local investigators [Time frame: Up to 22 weeks]
• CR as assessed by local investigators [Time frame: Up to 22 weeks]
• Duration of Response (DOR) as assessed by local investigators [Time frame: Up to 5 years]
• Odronextamab concentrations in serum when administered with CHOP [Time frame: Up to 22 weeks]
• Occurrence of Anti-Drug Antibodies (ADA) to odronextamab [Time frame: Up to 22 weeks]
• Magnitude of ADA to odronextamab [Time frame: Up to 22 weeks]
• PFS assessed by local investigator review [Time frame: Up to 5 years]
• EFS assessed by local investigator review [Time frame: Up to 5 years]
• BOR assessed by ICR [Time frame: Up to 22 weeks]

Eligibility criteria

Inclusion criteria

• Previously untreated participants for lymphoma with documented Cluster of Differentiation 20+ (CD20+) DLBCL, as described in the protocol OR relapsed or refractory DLBCL, for whom next available standard of care therapy is not available or deemed ineligible according to the 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.

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 Relapsed/Refractory (R/R) DLBCL and participants with DLBCL transformed from an indolent 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 Inclusion/ Exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 23 centers

• Mayo Clinic - Arizona — Scottsdale
• David Geffen School of Medicine at UCLA — Los Angeles
• University of California Irvine Medical Center — Orange
• University of California (UC) Davis — Sacramento
• Mayo Clinic Jacksonville — Jacksonville
• Indiana University Melvin and Bren Simon Comprehensive Cancer Center — Indianapolis
• St Vincent Ascension at Peyton Manning Childrens Hospital — Indianapolis
• Investigative Clinical Research of Indiana — Noblesville
• … and 15 more centers

Spain · 22 centers

Center list to be confirmed — check the primary protocol.

France · 19 centers

• Centre Hospitalier de Cornouaille Quimper Concarneau — Quimper
• Centre Hospitalier Universitaire (CHU) Rennes — Rennes
• CHRU de Tours — Tours
• Polyclinique Bordeaux Nord Aquitaine — Bordeaux
• Centre Hospitalier Universitaire (CHU) de Bordeaux — Pessac
• Centre Hospitalier Universitaire De Poitiers — Poitiers
• Hopital Saint Vincent-de-Paul — Lille
• Nantes University Hospital — Nantes
• … and 11 more centers

Italy · 15 centers

Center list to be confirmed — check the primary protocol.

South Korea · 11 centers

Center list to be confirmed — check the primary protocol.

Germany · 10 centers

• Robert-Bosch-Krankenhaus — Stuttgart
• Kliniken Ostalb Stauferklinikum Schwab Gmund — Mutlangen
• Clinic Frankfurt (Oder) — Frankfurt am Main
• University Hospital Essen — Essen
• Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR — Mainz
• UKS Homburg — Homburg
• Hematological Praxis Dresden — Dresden
• Vivantes Klinikum Am Urban — Berlin
• … and 2 more centers

Poland · 10 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 9 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 7 centers

Center list to be confirmed — check the primary protocol.

Austria · 6 centers

• Landeskrankenhaus Hochsteiermark — Leoben
• Kepler University Hospital — Linz
• Medical University Graz — Graz
• Medical University of Vienna — Vienna
• Hanusch Krankenhaus — Vienna
• Klinikum Wels-Grieskirchen — Wels

Israel · 6 centers

• The Chaim Sheba Medical Center — Tel Litwinsky
• Samson Assuta Ashdod University Hospital — Ashdod
• … and 4 more centers

Australia · 5 centers

• Liverpool Hospital — Liverpool
• Calvary Mater Newcastle — Waratah
• Icon Cancer Centre - Wesley — Auchenflower
• Pindara Private Hospital — Benowa
• Epworth Freemasons — East Melbourne

Belgium · 5 centers

• AZ St.-Elisabeth Herentals vzw — Herentals
• Centre Hospitalier Regional de Verviers — Verviers
• Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital — Ghent
• Az Delta — Roeselare
• Institut Jules Bordet — Brussels

Malaysia · 5 centers

Center list to be confirmed — check the primary protocol.

Chile · 4 centers

• Hospital Clinico Universidad de Los Andes — Santiago
• Centro Oncologia de Precision Universidad Mayor — Santiago
• Inmunocel — Santiago
• Clinica Alemana de Santiago — Santiago

Czechia · 4 centers

• University Hospital Hradec Kralove — Hradec Králové
• University Hospital Brno — Brno
• University Hospital Kralovske Vinohrady — Prague
• Vseobecna Fakultni Nemocnice V Praze — Prague

Thailand · 4 centers

Center list to be confirmed — check the primary protocol.

Singapore · 3 centers

Center list to be confirmed — check the primary protocol.

Ireland · 2 centers

• Beaumont Hospital — Dublin
• St James Hospital and Trinity College Dublin — Dublin

United Kingdom · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06091865 · R1979-ONC-2105 · 2022-502785-25-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗