Clinical trial NCT06097364: A Trial to Learn if Odronextamab Combined With Chemotherapy is Safe and Well-Tolerated and How Well it Works Compared to Rituximab Combined With Chemotherapy for Adult Participants With Follicular Lymphoma
Official title: A Phase 3, Open-Label, Randomized Study to Compare the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20x Anti-CD3 Bispecific Antibody, Combined With Chemotherapy Versus Rituximab Combined With Chemotherapy in Previously Untreated Participants With Follicular Lymphoma (OLYMPIA-2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Follicular Lymphoma (FL)
Keywords: Non-Hodgkin lymphomas (NHL)
Relapsed or Refractory (R/R) FL
B-cells NHL (B-NHL)
Untreated FL
Odronextamab
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-10-24
Enrollment: 733
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. The study is focused on participants with previously untreated follicular lymphoma. Follicular lymphoma is a type of non-Hodgkin lymphoma or NHL. Participants with follicular lymphoma that has come back after treatment (called "relapsed") or did not respond to treatment (called "refractory") are eligible to take part only in Part 1A of the study.

This study is made up of 3 parts: Part 1A (non-randomized), Part 1B and Part 2 (randomized - controlled).

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 to be used in Part 2 of the study.

The aim of Part 2 of the study is to assess 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 for 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
* 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. Have diagnosis of cluster of differentiation 20 positive (CD20+) FL grade 1-3a, stage II bulky or stage III / IV

   1. For Part 1A: previously untreated participants who have Follicular Lymphoma International Prognostic Index (FLIPI)-1 score of 3 to 5, or R/R FL
   2. For Part 1B: previously untreated participants who have FLIPI-1 score of 3 to 5
   3. For Part 2: previously untreated participants who have FLIPI-1 score of 0 to 5
2. Have measurable disease on cross sectional imaging documented by diagnostic computed tomography \[CT\], or magnetic resonance imaging \[MRI\] imaging, as described in the protocol
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
4. Adequate bone marrow and hepatic function.

Key Exclusion Criteria:

1. Participants with central nervous system lymphoma or leptomeningeal lymphoma
2. Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
3. Participants with Waldenström macroglobulinemia (WM, lymphoplasmacytic lymphoma), grade 3b follicular lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma
4. Recent major surgery and history or organ transplantation
5. A malignancy other than NHL unless the participant is adequately and definitively treated and any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, as described in the protocol.

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with chemotherapy
timeFrame: Up to 35 days
measure: Incidence of treatment-emergent adverse events (TEAEs) of odronextamab in combination with chemotherapy
timeFrame: Up to 2 years
measure: Severity of TEAEs of odronextamab in combination with chemotherapy
timeFrame: Up to 2 years
measure: Complete Response rate at 30 months (CR30) assessed by independent central review (ICR)
timeFrame: Up to 30 months
Secondary outcomes:
measure: Odronextamab concentrations in serum when administered with chemotherapy
timeFrame: Up to 30 months
measure: Odronextamab concentrations in serum when administered as monotherapy
timeFrame: Up to 30 months
measure: Incidence of anti-odronextamab antibodies (ADAs)
timeFrame: Up to 30 months
measure: Titers of ADAs to odronextamab
timeFrame: Up to 30 months
measure: Incidence of neutralizing antibodies (NAb) to odronextamab
timeFrame: Up to 30 months
measure: Best overall response (BOR) as assessed by the investigator
timeFrame: Up to 30 months
measure: Progression free survival (PFS) as assessed by ICR
timeFrame: Up to 5 years
measure: CR30 as assessed by local investigator
timeFrame: Up to 30 months
measure: Change in patient reported physical functioning scale scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC-QLQ-C30)
timeFrame: Up to 5 years
measure: PFS as assessed by local investigator
timeFrame: Up to 5 years
measure: Event-free survival (EFS) as assessed by ICR
timeFrame: Up to 5 years
measure: EFS as assessed by local investigator
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: BOR as assessed by local investigator
timeFrame: Up to 30 months
measure: BOR as assessed by ICR
timeFrame: Up to 30 months
measure: Duration of response (DOR) assessed by ICR
timeFrame: Up to 5 years
measure: DOR as assessed by local investigator
timeFrame: Up to 5 years
measure: Time to next anti-lymphoma treatment (TTNT)
timeFrame: Up to 5 years
measure: Incidence of TEAEs
timeFrame: Up to 2 years
measure: Severity of TEAEs
timeFrame: Up to 2 years
measure: Change in patient reported health related quality of life (HRQoL) as measured by EORTC-QLQ-C30
timeFrame: Up to 5 years
measure: Change in cancer disease as measured by EORTC-QLQ-C30
timeFrame: Up to 5 years
measure: Change in treatment related symptoms as measured by EORTC-QLQ-C30
timeFrame: Up to 5 years
measure: Change in patient-reported lymphoma disease as measured by the Lymphoma Subscale of the Functional Assessment of Cancer Treatment-Lymphoma (FACT-LymS)
timeFrame: Up to 5 years
measure: Change in treatment-related symptoms as measured by the FACT-LymS
timeFrame: Up to 5 years
measure: Change in patient-reported general health status per EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
timeFrame: Up to 5 years
measure: Change in patient-reported treatment side effects burden per Functional Assessment of Cancer Therapy-General Global Population Item 5 (FACT-G GP5)
timeFrame: Up to 5 years
measure: Change in Patient Global Impression of Severity (PGIS)
timeFrame: Up to 5 years
measure: Change in Patient Global Impression of Change (PGIC)
timeFrame: Up to 5 years
measure: Change in score of the FACT-G GP5 item in the patient population
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Plantation
country: United States
facility: Boca Raton Clinical Research (BRCR) Global
state: Florida
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: 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: Westbury
country: United States
facility: Clinical Research Alliance Inc
state: New York
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: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Saint Poelten
country: Austria
facility: Karl Landsteiner University Hospital St. Poelten
state: Lower Austria
city: Graz
country: Austria
facility: Medical University of Graz
state: Styria
city: Leoben
country: Austria
facility: Landeskrankenhaus Hochsteiermark
state: Styria
city: Linz
country: Austria
facility: Kepler University Hospital
state: Upper Austria
city: Innsbruck
country: Austria
facility: Innsbruck Medical University
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen
city: Sint Niklaas
country: Belgium
facility: Verenigde Ziekenhuizen van Waas en Durme
state: Oost Vlaanderen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital
state: Oost-Vlaanderen
city: Bruges
country: Belgium
facility: Algemeen Ziekenhuis St Jan Brugge Oostende Av
state: West Flanders
city: Kortrijk
country: Belgium
facility: AZ Groeninge
state: West Flanders
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Liege
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Brasilia
country: Brazil
facility: Hospital Sirio Libanes Brasilia
state: Distrito Federal
city: Belo Horizonte
country: Brazil
facility: Instituto Mario Pena de Ensino Pesquisa e Inovacao
state: Minas Gerais
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Cancer
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: AC Camargo Cancer Center
city: Sao Paulo
country: Brazil
facility: Casa de Saude Santa Marcelina
city: Santiago
country: Chile
facility: Hospital Clinico Universidad de Los Andes
state: Las Condes
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile
state: Region Metropolitana
city: Santiago
country: Chile
facility: Centro Oncologia de Precision Universidad Mayor
state: Region Metropolitana
city: Santiago
country: Chile
facility: Inmunocel
state: Region Metropolitana
city: Hradec Kralove
country: Czechia
facility: University Hospital Hradec Kralove
state: North Central Czech Republic
city: Brno
country: Czechia
facility: University Hospital Brno
state: South Moravian
city: Cannes
country: France
facility: Cannes Hospital (Centre Hospitalier Cannes Simone Veil)
state: Alpes Maritimes
city: Tours
country: France
facility: CHRU de Tours
state: Centre Val De Loire
city: Nimes
country: France
facility: Institut de Cancerologie du Gard
state: Gard
city: Argenteuil
country: France
facility: Hopital Victor Dupouy Argenteuil
state: Ile De France
city: Mont de Marsan
country: France
facility: Centre Hospitalier de Mont-de-Marsan
state: Nouvelle Aquitaine
city: Nantes
country: France
facility: Nantes University Hospital
state: Pays De La Loire
city: Cergy Pontoise
country: France
facility: The Novo Hospital North West Val Deoise
state: Pontoise
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire de Grenoble
city: Le Puy-en-Velay
country: France
facility: Centre Hospitalier Emile Roux
city: Lens
country: France
facility: Centre Hospitalier de Lens (Centre Hospitalier Dr Schaffner dLens)
city: Paris
country: France
facility: Hopital Saint Louis
city: Pessac
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier Sud - Hôpital Haut Lévêque
city: Saint Nazaire
country: France
facility: Centre Hospitalier de Saint Nazaire
city: Saint-Etienne
country: France
facility: CHU de Saint-Etienne
city: Kiel
country: Germany
facility: Stadtisches Krankenhaus Kiel
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
state: Yerushalayim
city: Be'er Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: The Tel Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Assuta Medical Centers
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
state: Forli Cesena
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino
state: Piemonte
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: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia
city: Pisa
country: Italy
facility: University of Pisa, Section of Hematology
city: Potenza
country: Italy
facility: Azienda Ospedaliera Regionale San Carlo
city: Ravenna
country: Italy
facility: UO Ematologia Ravenna
city: Reggio Emilia
country: Italy
facility: Azienda Unita Sanitaria Locale Irccs Arcispedale Santa Maria Nuova
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria del Friuli Centrale
city: Krakow
country: Poland
facility: Matopolskie Centrum Medyczne S.C.
state: Malopolskie
city: Skorzewo
country: Poland
facility: Aidport
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: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. Mikolaja Kopernika w Lodzi (Copernicus Memorial Hospital)
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: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy Warszawa
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalusia
city: Oviedo
country: Spain
facility: Hospital Universitario Central De Asturias
state: Asturias
city: Sabadell
country: Spain
facility: Parc Tauli Sabadell Hospital Universitari
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua Terrassa
state: Barcelona
city: Alicante
country: Spain
facility: Hospital General Universitario Doctor Balmis Alicante
state: Comunidad Valenciana
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Salud Madrid
state: Madrid
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Ourense
country: Spain
facility: Complexo Hospitalario Universitario de Ourense
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra- Pamplona
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Toledo
country: Spain
facility: Hospital General Universitario de Toledo
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Hospital Kaohsiung
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Multipal Wan Fang University
city: Bangkok
country: Thailand
facility: Chulalongkorn University
state: Krung Thep Maha Nakhon [Bangko]
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
city: Yenimahalle
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital
state: Ankara
city: Ankara
country: Turkey
facility: Gazi University
state: Central Anatolia
city: Mezitli
country: Turkey
facility: VM Medical Park Mersin Hospital
state: Mersin
city: Sakarya
country: Turkey
facility: Sakarya University
state: Serdivan
city: Tekirdag
country: Turkey
facility: Tekirdag Namik Kemal University Hospital
state: Suleymanpasa
city: Ankara
country: Turkey
facility: Liv Hospital Ankara
city: Istanbul
country: Turkey
facility: VKV American Hopital
city: Istanbul
country: Turkey
facility: Istanbul University
city: Kayseri
country: Turkey
facility: Erci̇yes Uni̇versi̇ty
city: Samsun
country: Turkey
facility: Ondokuz Mayıs University
city: Zonguldak
country: Turkey
facility: Zonguldak Bulent Ecevit University
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
state: Cornwall
city: Uxbridge
country: United Kingdom
facility: The Hillingdon Hospitals NHS Foundation Trust
state: London
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: West Midlands
city: Aberdeen
country: United Kingdom
facility: NHS Grampian: Aberdeen Royal Infirmary
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: