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

Diffuse Large B-cell Lymphoma (DLBCL) Clinical Trial

— OLYMPIA-3  

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 (O-CHOP) Versus Rituximab in Combination With CHOP (R-CHOP) in Previously Untreated Participants With Diffuse Large B-cell Lymphoma (DLBCL) (OLYMPIA-3)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06091865
• Other study ID #: R1979-ONC-2105
• Secondary ID: 2022-502785-25-0
• Status: Recruiting
• Phase: Phase 3
• Start date: December 13, 2023
• Est. completion date: September 18, 2028

Study information

• Verified date: March 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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"), have come back after treatment (called "relapsed"), or have not responded to treatment (called "refractory").

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 and chemotherapy, the current standard of care treatment approved for Non-Hodgkin's lymphoma (NHL). 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 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)

• The impact from the study drug on your quality of life and ability to complete routine daily activities

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 904
• Est. completion date: September 18, 2028
• Est. primary completion date: September 18, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

KEY Inclusion Criteria:

1. Previously untreated participants for lymphoma with documented cluster of differentiation 20+ (CD20+) DLBCL, as described in the protocol OR relapsed or refractory DLBCL (Part 1A only)

2. Measurable disease with at least one nodal lesion or at least one extranodal lesion, as described in the protocol

3. Eastern Cooperative Oncology Group (ECOG) performance status =2

4. Life expectancy = 12 months

5. International Prognostic Index (IPI) of 3 to 5 (part 1 only) and =2 (part 2) for untreated DLBCL only;

6. Adequate hematologic and organ function, as defined in the protocol.

KEY Exclusion Criteria:

1. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL and history or current relevant CNS pathology

2. Another active malignancy, significant active disease or medical condition, as described in the protocol

3. Peripheral neuropathy Grade =3

4. Treatment with any systemic anti-lymphoma therapy

5. Any investigational therapy within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment

6. Recent major surgery, prior organ transplantation, or standard radiotherapy, as described in the protocol

7. Allergy/hypersensitivity to study drugs, as described in the protocol

8. 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

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma (DLBCL)
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

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

Locations

Country	Name	City	State
Australia	Icon Cancer Centre	Auchenflower	Queensland
Australia	Epworth Freemasons	East Melbourne	Victoria
Austria	Klinikum Wels-Grieskirchen GmbH	Wels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital	Gent	Oost-Vlaanderen
Belgium	Az st Elizabeth	Herentals
Belgium	AZ Delta	Roeselare	West Flanders
Belgium	CHR de Verviers	Verviers
Chile	Clinica Alemana de Santiago	Santiago	Región Metropolitana
Chile	Hospital Clinico Universidad de Los Andes	Santiago	Las Condes
Chile	Inmunocel	Santiago	Region Metropolitana
Czechia	University Hospital Hradec Kralove	Hradec Kralove 5
Czechia	University Hospital Kralovske Vinohrady	Prague
Czechia	Vseobecna fakultni nemocnice v Praze	Praha
France	Centre Hospitalier Universitaire Angers (CHU Angers)	Angers
France	Hopital Victor Dupouy Argenteuil	Argenteuil	Île De France
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux Cedex	Gironde
France	Centre Hospitalier Metropole Savoie	Chambery	Savoie
France	Hôpital Saint Vincent-de-Paul	Lille cedex	Nord
France	Change Annecy	Metz Tessy
France	CHU Nimes Institut de Cancerologie	Nimes
France	Saint Antoine Hospital	Paris
France	Centre Hospitalier Universitaire (CHU) de Bordeaux	Pessac	Nouvelle-Aquitaine
France	CHU de Poitiers	Poitiers	Nouvelle Aquitaine
France	Centre Hospitalier Universitaire (CHU) Rennes	Rennes	Bretagne
France	CHU de Saint-Etienne	Saint-Etienne
France	CHRU de Tours	Tours	Centre Val De Loire
France	Gustave Roussy	Villejuif	Paris
Germany	Hematological Praxis Dresden	Dresden	Sachsen
Germany	Clinic Frankfurt (Oder)	Oder
Israel	The Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei tumori	Meldola (fc)	Forli-Cesena
Italy	Istituto Europeo di Oncologia	Milano
Italy	ASST Monza Ospedale San Gerardo	Monza
Italy	Federico II University	Napoli
Italy	Azienda Ospedaliero Universitaria Maggiore della Carita	Novara
Italy	Ospedale Santa Maria delle Croci	Ravenna
Italy	Azienda Sanitaria Universitaria Friuli Centrale	Udine
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Yeyungnam University Medical Center	Daegu
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul st mary's hospital	Seoul
Korea, Republic of	The Catholic University of Korea	Seoul
Korea, Republic of	St. Vincent Hospital, The Catholic University of Korea	Suwon-si	Gyeonggi-do
Poland	Malopolskie Centrum Medyczne	Krakow	Malopolskie
Poland	Pratia Poznan Medical Center	Poznan	Wielkopolska
Singapore	Tan Tock Seng Hospital	Singapore
Spain	Hospital Sant Pau	Barcelona
Spain	Hospital Virgen de Las Nieves de Granada	Granada
Spain	Fundacion Jimenez Diaz University Hospital	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Central De Asturias	Oviedo	Asturias
Spain	Son Espases University Hospital	Palma	Balearic Islands
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcón	Madrid
Spain	Hospital Universitari Parc Tauli	Sabadell	Barcelona
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Clinico Universitario Santiago de Compostela	Santiago de Compostela	A Coruna
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitari Mutua Terrassa	Terrassa	Barcelona
Spain	Hospital General Universitario de Toledo	Toledo
Spain	Instituto Valenciano de Oncologia	Valencia
Spain	University Hospital Doctor Peset	Valencia
Thailand	Chulalongkorn University	Bangkok	Krung Thep Maha Nakhon [Bangko]
Thailand	Sriraj Hospital	Bangkok
Thailand	Chiang Mai University	Chiang Mai
Thailand	Khon Kaen University	Khon Kaen
Turkey	Gazi Universitesi	Besevler
Turkey	Istanbul University, Istanbul Faculty of Medicine	Istanbul
Turkey	Dokuz Eylul University	Izmir
Turkey	Ege University	Izmir
Turkey	Sakarya University Medical Faculty Hematology Department	Sakarya
Turkey	Tekirdag Namik Kemal University Hospital	Tekirdag	Suleymanpasa
Turkey	Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital	Yenimahalle	Ankara
United Kingdom	NHS Grampian: Aberdeen Royal Infirmary	Aberdeen
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	Center For Oncology and Blood Disorders	Houston	Texas
United States	Indiana University Melvin and Bren Simon Comprehensive Cancer Center	Indianapolis	Indiana
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Clinical Research of Indiana	Noblesville	Indiana
United States	The Community Cancer Trials	Ogden	Utah
United States	UC Irvine Health Chao Family Comprehensive Cancer Cente	Orange	California
United States	Stony Brook University Hospital	Stony Brook	New York
United States	ProHealth Care Inc	Waukesha	Wisconsin
United States	Clinical Research Alliance Inc	Westbury	New York

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Chile,  Czechia,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Poland,  Singapore,  Spain,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities (DLTs)	Part 1	Up to 35 days
Primary	Incidence of treatment emergent adverse events (TEAEs)	Part 1	Up to 2 years
Primary	Severity of TEAEs	Part 1	Up to 2 years
Primary	Progression free survival (PFS), assessed by independent central review (ICR)	Part 2	Up to 5 years
Secondary	Event-free survival (EFS) assessed by ICR	Part 2	Up to 5 years
Secondary	Complete response (CR) assessed by ICR	Part 2	Up to 22 weeks
Secondary	Overall survival (OS)	Part 2	Up to 5 years
Secondary	Best Overall response (BOR) as assessed by local investigators	Part 1 and Part 2	Up to 22 weeks
Secondary	CR as assessed by local investigators	Part 1 and Part 2	Up to 22 weeks
Secondary	Duration of response (DOR) as assessed by local investigators	Part 1 and Part 2	Up to 5 years
Secondary	Odronextamab concentrations in serum when administered with CHOP	Part 1 and Part 2	Up to 22 weeks
Secondary	Incidence of anti-drug antibodies (ADA) to odronextamab when administered with CHOP	Part 1 and Part 2	Up to 22 weeks
Secondary	Titer of ADA to odronextamab when administered with CHOP	Part 1 and Part 2	Up to 22 weeks
Secondary	Incidence of neutralizing antibodies (NAb) to odronextamab when administered with CHOP	Part 1 and Part 2	Up to 22 weeks
Secondary	PFS assessed by local investigator review	Part 2	Up to 5 years
Secondary	EFS assessed by local investigator review	Part 2	Up to 5 years
Secondary	BOR assessed by ICR	Part 2	Up to 22 weeks
Secondary	DOR assessed by ICR	Part 2	Up to 5 years
Secondary	Incidence of TEAEs	Part 2	Up to 2 years
Secondary	Severity of TEAEs	Part 2	Up to 2 years
Secondary	Measurable Residual Disease (MRD) status	Part 2	Up to 22 weeks
Secondary	Duration of MRD-negativity	Part 2	Up to 5 years
Secondary	Change in physical functioning as measured by EORTC QLQ C30	Part 2 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.	Up to 5 years
Secondary	Change from baseline of patient reported outcomes, as measured by European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C) 30	Part 2 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.	Up to 5 years
Secondary	Change from baseline of patient reported outcomes, as measured by Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS)	Part 2 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.	Up to 5 years
Secondary	Change from baseline of patient reported outcomes, as measured by Patient Global Impression of Severity (PGIS)	Part 2 The PGIS includes a single-item to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. Patients will choose the response that best describes the severity of their overall cancer symptoms with options on a 5-point scale ranging from 1 (No symptoms) to 4 (Very Severe).	Up to 5 years
Secondary	Change from baseline of patient reported outcomes, as measured by Patient Global Impression of Change (PGIC)	Part 2 The PGIC item includes a single-item to assess how a patient perceives their overall change in health status since the start of study treatment. Patients will choose from response options on a 7-point scale ranging from 1 (Much Better) to 7 (Much worse); 1- Much Better, 2-Moderately Better, 3-A Little Better, 4-About the Same, 5-A Little Worse, 6-Moderately Worse, 7-Much Worse.	Up to 5 years
Secondary	Change from baseline of patient reported outcomes, as measured by EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)	Part 2 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".	Up to 5 years
Secondary	Change in score of the Functional Assessment of Cancer Therapy-General (FACT-G ) GP5 item	Part 2 A single item (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).	Up to 5 years