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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03888105




Registration number
NCT03888105
Ethics application status
Date submitted
14/03/2019
Date registered
25/03/2019
Date last updated
8/04/2024

Titles & IDs
Public title
A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Patients With B-cell Non-Hodgkin Lymphoma That Have Been Previously Treated
Scientific title
An Open-Label Study to Assess the Anti-Tumor Activity and Safety of REGN1979, an Anti CD20 x Anti-CD3 Bispecific Antibody, in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Secondary ID [1] 0 0
2017-002139-41
Secondary ID [2] 0 0
R1979-ONC-1625
Universal Trial Number (UTN)
Trial acronym
ELM-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Non-Hodgkin Lymphoma (NHL) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Odronextamab

Experimental: FL - Follicular lymphoma grade 1-3a cohort

Experimental: DLBCL - Diffuse large B-cell lymphoma cohort

Experimental: MCL - Mantle Cell Lymphoma cohort

Experimental: MZL - Marginal Zone Lymphoma cohort

Experimental: Other B-NHL - Other B-cell non-Hodgkin lymphoma cohort (excluding FL Grade 1-3a, DLBCL, MCL, MZL, Waldenström macroglobulinemia [WM]); Patients with a current diagnosis of mixed histology of B-NHL with an aggressive component (such as concurrent FL and DLBCL) will be allowed


Treatment: Drugs: Odronextamab
Administered by intravenous (IV) infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
ORR (FL grade 1-3a/MZL)
Timepoint [1] 0 0
From first patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study
Primary outcome [2] 0 0
ORR (DLBCL/MCL/Other B-NHL)
Timepoint [2] 0 0
From first patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study
Secondary outcome [1] 0 0
ORR (FL/MZL)
Timepoint [1] 0 0
First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.
Secondary outcome [2] 0 0
ORR (DLBCL/MCL/Other B-NHL)
Timepoint [2] 0 0
First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.
Secondary outcome [3] 0 0
CR rate (FL grade 1-3a/MZL)
Timepoint [3] 0 0
First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.
Secondary outcome [4] 0 0
CR rate (DLBCL/MCL/Other B-NHL)
Timepoint [4] 0 0
First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.
Secondary outcome [5] 0 0
PFS
Timepoint [5] 0 0
First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary outcome [6] 0 0
OS
Timepoint [6] 0 0
First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary outcome [7] 0 0
DOR
Timepoint [7] 0 0
First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary outcome [8] 0 0
DCR (FL grade 1-3a/MZL)
Timepoint [8] 0 0
First patient first dose until all patients have completed 52 weeks of study treatment or have withdrawn from the study.
Secondary outcome [9] 0 0
DCR (DLBCL/MCL/Other B-NHL)
Timepoint [9] 0 0
First patient first dose until all patients have completed 36 weeks of study treatment or have withdrawn from the study.
Secondary outcome [10] 0 0
Incidence and severity of treatment emergent adverse events (TEAEs)
Timepoint [10] 0 0
First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary outcome [11] 0 0
Pharmacokinetics: Concentration of odronextamab
Timepoint [11] 0 0
12 weeks following end of treatment
Secondary outcome [12] 0 0
Incidence of anti-drug antibodies (ADA) to odronextamab over time
Timepoint [12] 0 0
12 weeks following end of treatment
Secondary outcome [13] 0 0
Titer of anti-drug antibodies to odronextamab over time
Timepoint [13] 0 0
12 weeks following end of treatment
Secondary outcome [14] 0 0
Incidence of neutralizing antibodies (Nab) to odronextamab over time
Timepoint [14] 0 0
12 weeks following end of treatment
Secondary outcome [15] 0 0
Changes in scores of patient-reported outcomes as measured by EORTC QLQ-C30
Timepoint [15] 0 0
First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary outcome [16] 0 0
Changes in scores of patient-reported outcomes as measured by FACT-Lym
Timepoint [16] 0 0
First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose
Secondary outcome [17] 0 0
Changes in scores of patient-reported outcomes as measured by EQ-5D-3L
Timepoint [17] 0 0
First patient first dose to disease progression or death due to any cause, whichever comes first, approximately 194 weeks following the first dose

Eligibility
Key inclusion criteria
Key

- For the FL grade 1-3a cohort only: Central histopathologic confirmation of the FL
Grade 1 to 3a diagnosis must be obtained before study enrollment. Patients with FL
grade 3b are ineligible for this cohort but may be included in the "other B-NHL"
cohort. Follicular lymphoma subtyping is based on the World Health Organization (WHO)
classification (Swerdlow, 2017).

- Disease-specific cohorts that has relapsed after or is refractory to at least 2 prior
lines of systemic therapy as defined in the protocol

- DLBCL cohort: Patients with DLBCL that has relapsed after or is refractory to at least
2 prior lines of systemic therapy as defined in the protocol

- MCL after BTK inhibitor therapy cohort: New enrollment is paused until further notice

- MZL cohort: Patients with MZL that have relapsed or is refractory to at least 2 prior
lines of systemic therapy.

- Other B-NHL cohort: Patients with B-NHL other than FL grade 1-3a, DLBCL, MCL, or MZL
that has relapsed after or is refractory to at least 2 prior lines of systemic therapy
as defined in the protocol. New enrollment stopped for patients with Burkitt lymphoma
and Burkitt-like lymphoma.

- Patients should in the judgment of the investigator require systemic therapy for
lymphoma at the time of study enrollment

- Measurable disease on cross sectional imaging as defined in the protocol documented by
diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI)

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Adequate bone marrow, hepatic, and renal function as defined in the protocol

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS
Non-Hodgkin Lymphoma (NHL) (suspected CNS lymphoma should be evaluated by lumbar
puncture, as appropriate, in addition to the mandatory head CT or MRI).

- Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 28
days prior to first administration of study drug, whichever is shorter.

- History of allogeneic stem cell transplantation

- Prior treatment with any chimeric antigen receptor T-cell (CAR-T) therapy

- Continuous systemic corticosteroid treatment with more than 10 mg per day of
prednisone or anti-inflammatory equivalent within 72 hours of start of study drug

- History of neurodegenerative condition or CNS movement disorder. Patients with a
history of seizure within 12 months prior to study enrollment are excluded

- Another malignancy except B-NHL in the past 5 years, with the exception of
non-melanoma skin cancer that has undergone potentially curative therapy or in situ
cervical carcinoma, or any other tumor that has been deemed to be effectively treated
with definitive local control and with curative intent.

- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or
hepatitis C infection; cytomegalovirus (CMV) infection as noted by detectable levels
on a blood polymerase chain reaction (PCR) assay as defined in the protocol or other
uncontrolled infections

- Known hypersensitivity to both allopurinol and rasburicase

- Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
5/02/2028
Actual
Sample size
Target
512
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Border Medical Oncology, Albury Wodonga Regional Cancer Centre - East Albury
Recruitment hospital [2] 0 0
Epworth Hospital - East Melbourne
Recruitment hospital [3] 0 0
Penninsula & South Eastern Haemotology and Oncology Group - Frankston
Recruitment hospital [4] 0 0
Andrew Love Cancer Center - Geelong
Recruitment hospital [5] 0 0
Olivia Newton John Cancer Centre - Heidelberg
Recruitment hospital [6] 0 0
The Tweed Hospital - Murdoch
Recruitment hospital [7] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [8] 0 0
Andrew Love Cancer Center - Tweed Heads
Recruitment postcode(s) [1] 0 0
NSW 2640 - East Albury
Recruitment postcode(s) [2] 0 0
VIC 3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
VIC 3199 - Frankston
Recruitment postcode(s) [4] 0 0
VIC 3220 - Geelong
Recruitment postcode(s) [5] 0 0
VIC 3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
NSW 2485 - Murdoch
Recruitment postcode(s) [7] 0 0
6000 - Perth
Recruitment postcode(s) [8] 0 0
VIC3220 - Tweed Heads
Recruitment outside Australia
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United States of America
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Illinois
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Iowa
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Kentucky
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Massachusetts
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Michigan
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Minnesota
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Missouri
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Texas
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Canada
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Alberta
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Canada
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Nova Scotia
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China
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Beijing
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China
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Henan
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China
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Jiangsu
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China
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Jilin
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Sichuan
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China
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Wuhan Hubei Province
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China
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Zhejiang
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Canton
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Chongqing
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Wuhan
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Xi'an
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Caen
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Créteil
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Lille
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Pessac
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Pierre Bénite
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Poitiers
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Chemnitz
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Halle
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Mutlangen
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Villingen-Schwenningen
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Bologna
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Firenze
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Livorno
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Milano
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Novara
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Perugia
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Ravenna
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Reggio Emilia
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San Giovanni Rotondo
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Terni
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Chuo ku
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Goyang-si
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Seoul
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Ulsan
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Gdynia
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Lodz
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Warszawa
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Barcelona
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Donostia
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L'Hospitalet de llobregat
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Madrid
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Marbella
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Spain
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Palma de Mallorca
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Palma
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Spain
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Salamanca
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Valencia
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Taiwan
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Kaohsiung
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Taiwan
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New Taipei City
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Taichung City
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Tainan City
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Tainan
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Taipei City
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Taiwan
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Taoyuan
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United Kingdom
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Cardiff
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Edinburgh
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London
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Plymouth
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Sutton
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Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Primary objective is to assess the anti-tumor activity of single agent odronextamab as
measured by the objective response rate (ORR) according to the Lugano Classification of
response in malignant lymphoma (Cheson, 2014) and as assessed by independent central review
in each of the following B-cell non-Hodgkin lymphoma (B-NHL) subgroups:

- In patients with follicular lymphoma (FL) grade 1-3a *1,2

- In patients with diffuse large B-cell lymphoma (DLBCL) *1,2

- In patients with mantle cell lymphoma (MCL) that has relapsed after or is refractory to
a BTK inhibitor. This cohort will also include patients who have relapsed or have
disease refractory to prior systemic therapy, or patients who have demonstrated
intolerance to BTK inhibitor therapy, and who have progressed after other systemic
therapy.

- In patients with marginal zone lymphoma (MZL) *1

- In patients with other B-NHL subtypes *1

Secondary objectives are:

- To assess the anti-tumor activity of single agent odronextamab in each of 5
disease-specific cohorts, as measured by:

- ORR according to the Lugano Classification and as assessed by local investigator
evaluation

- Complete response (CR) rate according to the Lugano Classification and as assessed local
by local investigator evaluation and independent central review

- Progression-free survival (PFS)*3

- Overall survival (OS)

- Duration of response (DOR)*3

- Disease control rate (DCR)*3

- To evaluate the safety and tolerability of odronextamab

- To assess the pharmacokinetics (PK) of odronextamab

- To assess the immunogenicity of odronextamab

- To assess the effect of odronextamab on patient reported outcomes, including
health-related quality of life (HRQL), as measured by the validated instruments European
Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC
QLQ-C30), Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym), and EuroQoL 5
Dimensions 3 Levels (EQ-5D-3L)

- 1 that has relapsed after or is refractory to at least 2 prior lines of systemic
therapy

- 2 including an anti-CD20 antibody and an alkylating agent

- 3 according to Lugano Classification and as assessed by independent central review
and local investigator evaluation
Trial website
https://clinicaltrials.gov/ct2/show/NCT03888105
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials Administrator
Address 0 0
Country 0 0
Phone 0 0
844-734-6643
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03888105