Clinical trial NCT06230224: A Trial to Learn How Effective and Safe Odronextamab is Compared to Standard of Care for Adult Participants With Previously Treated Aggressive B-cell Non-Hodgkin Lymphoma
Official title: A Phase 3, Randomized, Open Label Study Evaluating the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 x Anti-CD3 Bispecific Antibody, Versus Standard of Care Therapy in Participants With Relapsed/Refractory Aggressive B-cell Non-Hodgkin Lymphoma (OLYMPIA-4)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: B-Cell Non-Hodgkin Lymphoma (B-NHL)
Keywords: Non-Hodgkin lymphomas (NHLs)
Aggressive NHL
B-Cell Non-Hodgkin Lymphoma (B-NHL)
Odronextamab
Anti-CD20 × anti-CD3 bispecific antibody
Relapsed/Refractory NHL
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-01-30
Enrollment: 216
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 patients with previously treated aggressive B-cell non-Hodgkin lymphoma whose cancer has stopped responding to treatment (also known as 'refractory') or has returned (also known as 'relapsed'). The aim of the study is to see how safe, tolerable and effective the study drug is when given alone.

The study is looking at several other research questions, including:

* What side effects may happen from taking the study drug versus Standard of Care (SOC)
* 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)
* Comparing the impact from the study drug versus SOC on quality-of-life and ability to complete routine daily activities


Eligibility criteria: Key Inclusion Criteria:

1. Histologically proven aggressive B-NHL, as described in the protocol. Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed
2. Have primary refractory or relapse 12 months or less (≤) from initiation of frontline therapy Only patients who received 1 prior line of therapy containing an anti-Cluster of Differentiation 20 (CD20) antibody and anthracycline are allowed for enrollment
3. Have measurable disease with at least one nodal lesion with longer diameter (LDi) greater than 1.5 cm or at least one extranodal lesion with LDi greater than 1.0 cm, documented by diagnostic imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\])
4. Intent to proceed to autologous stem cell transplant (ASCT), as described in the protocol
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
6. Adequate hematologic and organ function.

Key Exclusion Criteria:

1. Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL, as described in the protocol
2. History of or current relevant CNS pathology, as described in the protocol
3. A malignancy other than NHL unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated
4. 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
5. Wash-out period from prior anti-lymphoma treatments and infections, as described in the protocol
6. Allergy/hypersensitivity to study drug, or excipients.

NOTE: Other protocol defined inclusion / exclusion criteria apply

Primary outcomes:
measure: Event-free survival (EFS) as assessed by independent central review
timeFrame: Assessed up to 3 years
Secondary outcomes:
measure: Progression free survival (PFS) as assessed by independent central review
timeFrame: Assessed up to 3 years
measure: Best overall response (BOR) as assessed by independent central review
timeFrame: Assessed up to 6 months
measure: Overall change in physical functioning as measured by scores of the physical function scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30)
timeFrame: Assessed up to 3 years
measure: EFS as assessed by local investigator
timeFrame: Assessed up to 3 years
measure: PFS as assessed by local investigator
timeFrame: Assessed up to 3 years
measure: BOR as assessed by local investigator
timeFrame: Assessed up to 6 months
measure: Complete response (CR) as assessed by independent central review
timeFrame: Assessed up to 6 months
measure: CR as assessed by local investigator
timeFrame: Assessed up to 6 months
measure: Duration of response (DOR) assessed by independent central review
timeFrame: Assessed up to 3 years
measure: DOR assessed by local investigator
timeFrame: Assessed up to 3 years
measure: Overall survival (OS)
timeFrame: Assessed up to 3 years
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Assessed up to 1 year
measure: Severity of TEAEs
timeFrame: Assessed up to 1 year
measure: Odronextamab concentrations in serum
timeFrame: Assessed up to 6 months
measure: Incidence of anti-drug antibodies (ADAs) to odronextamab over the study duration
timeFrame: Assessed up to 6 months
measure: Titers of ADAs to odronextamab over the study duration
timeFrame: Assessed up to 6 months
measure: Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration
timeFrame: Assessed up to 6 months
measure: Measurable residual disease (MRD) status
timeFrame: Assessed up to 6 months
measure: Duration of MRD-negativity, as determined by circulating tumor DNA (ctDNA)
timeFrame: Assessed up to 3 years
measure: Overall change in patient-reported outcomes, as measured by scores of the EORTCQLQ- C30
timeFrame: Assessed up to 3 years
measure: Overall change in patient-reported outcomes, as measured by scores of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-LymS)
timeFrame: Assessed up to 3 years
measure: Overall change in patient-reported outcomes, as measured by scores of the EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)
timeFrame: Assessed up to 3 years
measure: Overall change in score of the Global Population item 5 (GP5) of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire
timeFrame: Assessed up to 3 years
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Heidelberg
country: Australia
facility: Olivia Newton John Cancer Wellness & Research Centre
state: Victoria
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
state: Forli Cesena
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico (CRO), Aviano, National Cancer Institute
state: Province Of Pordenone
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Novara
country: Italy
facility: AOU Maggiore della Carita
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi Varese
city: Suwon-si
country: Korea, Republic of
facility: St. Vincent Hospital, The Catholic University of Korea
state: Gyeonggi-do
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnam-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Namdong-Gu
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: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Marys Hospital
city: Seoul
country: Korea, Republic of
facility: Yeouido St. Marys Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah Jhor Bahru
state: Johor
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth
state: Sabah
city: Kuala Lumpur
country: Malaysia
facility: Hospital Ampang
state: Selangor
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: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
city: Singapore
country: Singapore
facility: National University Hospital Singapore
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalusia
city: Palma
country: Spain
facility: Hospital Universitari Son Espases
state: Balearic Islands
city: Terrassa
country: Spain
facility: Hospital Universitari Mutua Terrassa
state: Barcelona
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
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: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: University Hospital Doctor Peset
city: Chiayi City
country: Taiwan
facility: Chang Gung Medical Foundation
state: Chianan Plain
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou Branch
state: Hunan Province
city: Changhua City
country: Taiwan
facility: Changhua Christian Hospital
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: Taichung
country: Taiwan
facility: Taichung General Veterans Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn University
city: Bangkok
country: Thailand
facility: Sriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
city: Ankara
country: Turkey
facility: Gazi University
state: Central Anatolia
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: Ankara
country: Turkey
facility: Sbu Dr.A.Y. Ankara Onkoloji Suam
city: Izmir
country: Turkey
facility: Ege University
city: Sakarya
country: Turkey
facility: Sakarya University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayıs University
city: Zonguldak
country: Turkey
facility: Zonguldak Bulent Ecevit Univesity
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: