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)
Summary
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
Arms & interventions
- DrugOdronextamab
Odronextamab will be administered by intravenous (IV) infusion
- DrugRituximab
Rituximab will be administered IV, or subcutaneously (SC)
- DrugCyclophosphamide
Cyclophosphamide will be administered IV as part of chemotherapy
- DrugDoxorubicin
Doxorubicin will be administered IV as part of chemotherapy
- DrugVincristine
Vincristine will be administered IV as part of chemotherapy
- DrugPrednisone/Prednisolone
Prednisone or prednisolone will be administered orally (PO) as part of chemotherapy
Outcome measures
Primary
Incidence of Dose Limiting Toxicities (DLTs)
Part 1A
Time frame: Up to 35 days
Incidence of Treatment Emergent Adverse Events (TEAEs)
Part 1
Time frame: Up to 2 years
Severity of TEAEs
Part 1
Time frame: Up to 2 years
Progression Free Survival (PFS), assessed by Independent Central Review (ICR)
Part 2
Time frame: Up to 5 years
Secondary
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
DOR assessed by ICR
Time frame: Up to 5 years
Incidence of TEAEs
Time frame: Up to 2 years
Severity of TEAEs
Time frame: Up to 2 years
Minimal Residual Disease (MRD) status
Time frame: Up to 22 weeks
Change in physical functioning as measured by European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C) 30
Time frame: Up to 5 years
Change in patient reported outcomes, as measured by EORTC QLQ-C30
Time frame: Up to 5 years
Change in patient reported outcomes, as measured by Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS)
Time frame: Up to 5 years
Change in patient reported outcomes, as measured by Patient Global Impression of Severity (PGIS)
Time frame: Up to 5 years
Change in patient reported outcomes, as measured by Patient Global Impression of Change (PGIC)
Time frame: Up to 5 years
Change in patient reported outcomes, as measured by EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)
Time frame: Up to 5 years
Change in score of the Functional Assessment of Cancer Therapy-General (FACT-G ) GP5 item
Time frame: Up to 5 years
Eligibility criteria
Study locations (20)
David Geffen School of Medicine at UCLA
Los Angeles, California, 90095
University of California Irvine Medical Center
Orange, California, 92868
University of California (UC) Davis
Sacramento, California, 95817
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
St Vincent Ascension at Peyton Manning Childrens Hospital
Indianapolis, Indiana, 46260
Investigative Clinical Research of Indiana
Noblesville, Indiana, 46062
University of Kentucky
Lexington, Kentucky, 40536
University of Maryland Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Henry Ford Health System
Detroit, Michigan, 48202
Cancer and Hematology Centers of Western Michigan
Grand Rapids, Michigan, 49503
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Stony Brook University Hospital
Stony Brook, New York, 11794
Clinical Research Alliance Inc
Westbury, New York, 11590
Duke University Medical Center
Durham, North Carolina, 27710
East Carolina University
Greenville, North Carolina, 27834
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Center for Oncology and Blood Disorders
Houston, Texas, 77030
Community Cancer Trials of Utah
Ogden, Utah, 84405
Prohealth Care Inc
Waukesha, Wisconsin, 53188