Clinical trial NCT06091865: 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
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diffuse Large B-cell Lymphoma (DLBCL)
Keywords: Non-Hodgkin lymphomas (NHL)
B-cell non-Hodgkin lymphomas (B-NHL)
Diffuse Large B-cell Lymphoma
Odronextamab
Anti-CD20 × anti-CD3 bispecific antibody
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-10-19
Enrollment: 904
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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, for whom next available standard of care therapy is not available or deemed ineligible according to the investigator (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, except for participants with relapsed/refractory (R/R) DLBCL and participants with DLBCL transformed from an indolent follicular lymphoma after treatment with systemic anti-lymphoma therapy.
5. 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
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

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs)
timeFrame: Up to 35 days
measure: Incidence of treatment emergent adverse events (TEAEs)
timeFrame: Up to 2 years
measure: Severity of TEAEs
timeFrame: Up to 2 years
measure: Progression free survival (PFS), assessed by independent central review (ICR)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Event-free survival (EFS) assessed by ICR
timeFrame: Up to 5 years
measure: Complete response (CR) assessed by ICR
timeFrame: Up to 22 weeks
measure: Overall survival (OS)
timeFrame: Up to 5 years
measure: Best Overall response (BOR) as assessed by local investigators
timeFrame: Up to 22 weeks
measure: CR as assessed by local investigators
timeFrame: Up to 22 weeks
measure: Duration of response (DOR) as assessed by local investigators
timeFrame: Up to 5 years
measure: Odronextamab concentrations in serum when administered with CHOP
timeFrame: Up to 22 weeks
measure: Incidence of anti-drug antibodies (ADA) to odronextamab over the study duration
timeFrame: Up to 22 weeks
measure: Titer of ADA to odronextamab over the study duration
timeFrame: Up to 22 weeks
measure: Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration
timeFrame: Up to 22 weeks
measure: PFS assessed by local investigator review
timeFrame: Up to 5 years
measure: EFS assessed by local investigator review
timeFrame: Up to 5 years
measure: BOR assessed by ICR
timeFrame: Up to 22 weeks
measure: DOR assessed by ICR
timeFrame: Up to 5 years
measure: Incidence of TEAEs
timeFrame: Up to 2 years
measure: Severity of TEAEs
timeFrame: Up to 2 years
measure: Measurable Residual Disease (MRD) status
timeFrame: Up to 22 weeks
measure: Duration of MRD-negativity
timeFrame: Up to 5 years
measure: Change in physical functioning as measured by European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C) 30
timeFrame: Up to 5 years
measure: Change in patient reported outcomes, as measured by EORTC QLQ-C30
timeFrame: Up to 5 years
measure: Change in patient reported outcomes, as measured by Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS)
timeFrame: Up to 5 years
measure: Change in patient reported outcomes, as measured by Patient Global Impression of Severity (PGIS)
timeFrame: Up to 5 years
measure: Change in patient reported outcomes, as measured by Patient Global Impression of Change (PGIC)
timeFrame: Up to 5 years
measure: Change in patient reported outcomes, as measured by EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)
timeFrame: Up to 5 years
measure: Change in score of the Functional Assessment of Cancer Therapy-General (FACT-G ) GP5 item
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Sacramento
country: United States
facility: University of California (UC) Davis
state: California
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Comprehensive Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: St Vincent Ascension at Peyton Manning Childrens Hospital
state: Indiana
city: Noblesville
country: United States
facility: Investigative Clinical Research of Indiana
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of Western Michigan
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance Inc
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Houston
country: United States
facility: Center for Oncology and Blood Disorders
state: Texas
city: Ogden
country: United States
facility: Community Cancer Trials of Utah
state: Utah
city: Waukesha
country: United States
facility: Prohealth Care Inc
state: Wisconsin
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Auchenflower
country: Australia
facility: Icon Cancer Centre - Wesley
state: Queensland
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: East Melbourne
country: Australia
facility: Epworth Freemasons
state: Victoria
city: Leoben
country: Austria
facility: Landeskrankenhaus Hochsteiermark
state: Styria
city: Linz
country: Austria
facility: Kepler University Hospital
state: Upper Austria
city: Graz
country: Austria
facility: Medical University Graz
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Vienna
country: Austria
facility: Hanusch Krankenhaus
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen
city: Herentals
country: Belgium
facility: AZ St.-Elisabeth Herentals vzw
state: Antwerp
city: Gent
country: Belgium
facility: Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital
state: Oost-Vlaanderen
city: Roeselare
country: Belgium
facility: Az Delta
state: West Vlaanderen
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Verviers
country: Belgium
facility: Centre Hospitalier Regional de Verviers
city: Santiago
country: Chile
facility: Hospital Clinico Universidad de Los Andes
state: Las Condes
city: Santiago
country: Chile
facility: Inmunocel
state: Region Metropolitana
city: Santiago
country: Chile
facility: Clinica Alemana de Santiago
city: Hradec Kralove
country: Czechia
facility: University Hospital Hradec Kralove
state: East Bohemia
city: Prague
country: Czechia
facility: University Hospital Kralovske Vinohrady
city: Praha
country: Czechia
facility: Vseobecna Fakultni Nemocnice V Praze
city: Rennes
country: France
facility: Centre Hospitalier Universitaire (CHU) Rennes
state: Bretagne
city: Tours
country: France
facility: CHRU de Tours
state: Centre Val De Loire
city: Bordeaux Cedex
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
state: Gironde
city: Argenteuil
country: France
facility: Hopital Victor Dupouy Argenteuil
state: Ile De France
city: Bobigny
country: France
facility: Avicenne Hospital
state: Ile De France
city: Lille
country: France
facility: Hopital Saint Vincent-de-Paul
state: Nord
city: Poitiers
country: France
facility: CHU de Poitiers
state: Nouvelle Aquitaine
city: Pessac
country: France
facility: Centre Hospitalier Universitaire (CHU) de Bordeaux
state: Nouvelle-Aquitaine
city: Nantes
country: France
facility: Nantes University Hospital
state: Pays De La Loire
city: Chambery
country: France
facility: Centre Hospitalier Metropole Savoie
state: Savoie
city: Villejuif
country: France
facility: Gustave Roussy
state: Val De Marne / Ile De France
city: Angers
country: France
facility: Centre Hospitalier Universitaire Angers
city: Metz Tessy
country: France
facility: Change Annecy
city: Nimes
country: France
facility: CHU Nimes Institut de Cancerologie
city: Paris
country: France
facility: Assistance Publique-Hopitaux de Paris (AP-HP)
city: Saint-Etienne
country: France
facility: CHU de Saint-Etienne
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
state: Baden-Wurttemberg
city: Mutlangen
country: Germany
facility: Kliniken Ostalb Stauferklinikum Schwab Gmund
state: Gmund
city: Frankfurt
country: Germany
facility: Clinic Frankfurt (Oder)
state: Hesse
city: Essen
country: Germany
facility: University Hospital Essen
state: Nordrhein Westfalen
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
state: Rheinland-Pfalz
city: Dresden
country: Germany
facility: Hematological Praxis Dresden
state: Sachsen
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
city: Kiel
country: Germany
facility: Stadtisches Krankenhaus Kiel
city: Dublin
country: Ireland
facility: Beaumont Hospital
state: Leinster
city: Dublin
country: Ireland
facility: St James Hospital and Trinity College Dublin
city: Tel-Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
state: Tel Aviv
city: Ashdod
country: Israel
facility: Samson Assuta Ashdod University Hospital
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center
city: Meldola (fc)
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
state: Forli Cesena
city: Monza
country: Italy
facility: ASST Monza Ospedale San Gerardo
state: Lombardy
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Modena
country: Italy
facility: A.O.U. di Modena
city: Napoli
country: Italy
facility: Federico II University
city: Novara
country: Italy
facility: AOU Maggiore della Carita
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Turin
country: Italy
facility: Hematology - Città della Salute e della Scienza di Torino
city: Udine
country: Italy
facility: Santa Maria della Misericordia
city: Suwon-si
country: Korea, Republic of
facility: St. Vincent Hospital - The Catholic University of Korea
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Namdong-Gu
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeyungnam University Medical Center
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yeouido St. Marys Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St Marys Hospital
city: Ampang
country: Malaysia
facility: Hospital Ampang
state: Pahang
city: Kuantan
country: Malaysia
facility: Hospital Tg Ampuan Afzan
state: Pahang
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth
state: Sabah
city: Subang Jaya
country: Malaysia
facility: Subang Jaya Medical Center
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
state: Wilayah Persekutuan Kuala Lumpur
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Matopolskie Centrum Medyczne S.C.
state: Malopolskie
city: Poznan
country: Poland
facility: Pratia Poznan Medical Center
state: Wielkopolska
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr2 Bydgoszcz
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Building of the Non-Invasive Medicine Center
city: Lublin
country: Poland
facility: Centrum Innowacyjnych Terapii Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
city: Walbrzych
country: Poland
facility: Szpital Szpecjalistyczny w Walbrzychu
city: Singapore
country: Singapore
facility: National University Hospital Singapore
city: Singapore
country: Singapore
facility: National Cancer Centre of Singapore
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario Santiago de Compostela
state: A Coruna
city: Oviedo
country: Spain
facility: Hospital Universitario Central De Asturias
state: Asturias
city: Palma
country: Spain
facility: Son Espases University Hospital
state: Balearic Islands
city: Sabadell
country: Spain
facility: Hospital Universitari Parc Tauli
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua Terrassa
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Sant Pau
city: Granada
country: Spain
facility: Hospital Virgen De Las Nieves De Granada
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro, Servicio de Hematologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Toledo
country: Spain
facility: Hospital General Universitario de Toledo
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: University Hospital Doctor Peset
city: Changhua City
country: Taiwan
facility: Changhua Christian Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital
city: Puzi City
country: Taiwan
facility: Chang Gung Medical Foundation Chia Yi Branch
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Wanfang Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital- Linkou Branch
city: Bangkok
country: Thailand
facility: Chulalongkorn University
state: Krung Thep Maha Nakhon [Bangko]
city: Bangkok
country: Thailand
facility: Sriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chaing Mai University
city: Khon Kaen
country: Thailand
facility: Faculty of Medicine
city: Yenimahalle
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
state: Ankara
city: Mezitli
country: Turkey
facility: VM Medical Park Mersin Hospital
state: Mersin
city: Tekirdag
country: Turkey
facility: Tekirdag Namik Kemal University Hospital
state: Suleymanpasa
city: Besevler
country: Turkey
facility: Gazi Universitesi
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Faculty of Medicine
city: Izmir
country: Turkey
facility: Ege University
city: Izmir
country: Turkey
facility: Dokuz Eylul University
city: Sakarya
country: Turkey
facility: Sakarya Universty Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
city: Aberdeen
country: United Kingdom
facility: NHS Grampian: Aberdeen Royal Infirmary
city: Uxbridge
country: United Kingdom
facility: The Hillingdon Hospitals NHS Foundation Trust
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: