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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06091865




Registration number
NCT06091865
Ethics application status
Date submitted
13/10/2023
Date registered
19/10/2023
Date last updated
30/10/2024

Titles & IDs
Public title
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
Scientific 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)
Secondary ID [1] 0 0
2022-502785-25-00
Secondary ID [2] 0 0
R1979-ONC-2105
Universal Trial Number (UTN)
Trial acronym
OLYMPIA-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B-cell Lymphoma (DLBCL) 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
Treatment: Drugs - Rituximab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Prednisone/Prednisolone

Experimental: Odronextamab + CHOP - Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B).

Active comparator: Rituximab + CHOP - Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP.


Treatment: Drugs: Odronextamab
Odronextamab will be administered by intravenous (IV) infusion

Treatment: Drugs: Rituximab
Rituximab will be administered IV, or subcutaneously (SC)

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide will be administered IV as part of chemotherapy

Treatment: Drugs: Doxorubicin
Doxorubicin will be administered IV as part of chemotherapy

Treatment: Drugs: Vincristine
Vincristine will be administered IV as part of chemotherapy

Treatment: Drugs: Prednisone/Prednisolone
Prednisone or prednisolone will be administered orally (PO) as part of chemotherapy
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to 35 days
Primary outcome [2] 0 0
Incidence of treatment emergent adverse events (TEAEs)
Timepoint [2] 0 0
Up to 2 years
Primary outcome [3] 0 0
Severity of TEAEs
Timepoint [3] 0 0
Up to 2 years
Primary outcome [4] 0 0
Progression free survival (PFS), assessed by independent central review (ICR)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Event-free survival (EFS) assessed by ICR
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Complete response (CR) assessed by ICR
Timepoint [2] 0 0
Up to 22 weeks
Secondary outcome [3] 0 0
Overall survival (OS)
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Best Overall response (BOR) as assessed by local investigators
Timepoint [4] 0 0
Up to 22 weeks
Secondary outcome [5] 0 0
CR as assessed by local investigators
Timepoint [5] 0 0
Up to 22 weeks
Secondary outcome [6] 0 0
Duration of response (DOR) as assessed by local investigators
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Odronextamab concentrations in serum when administered with CHOP
Timepoint [7] 0 0
Up to 22 weeks
Secondary outcome [8] 0 0
Incidence of anti-drug antibodies (ADA) to odronextamab over the study duration
Timepoint [8] 0 0
Up to 22 weeks
Secondary outcome [9] 0 0
Titer of ADA to odronextamab over the study duration
Timepoint [9] 0 0
Up to 22 weeks
Secondary outcome [10] 0 0
Incidence of neutralizing antibodies (NAb) to odronextamab over the study duration
Timepoint [10] 0 0
Up to 22 weeks
Secondary outcome [11] 0 0
PFS assessed by local investigator review
Timepoint [11] 0 0
Up to 5 years
Secondary outcome [12] 0 0
EFS assessed by local investigator review
Timepoint [12] 0 0
Up to 5 years
Secondary outcome [13] 0 0
BOR assessed by ICR
Timepoint [13] 0 0
Up to 22 weeks
Secondary outcome [14] 0 0
DOR assessed by ICR
Timepoint [14] 0 0
Up to 5 years
Secondary outcome [15] 0 0
Incidence of TEAEs
Timepoint [15] 0 0
Up to 2 years
Secondary outcome [16] 0 0
Severity of TEAEs
Timepoint [16] 0 0
Up to 2 years
Secondary outcome [17] 0 0
Measurable Residual Disease (MRD) status
Timepoint [17] 0 0
Up to 22 weeks
Secondary outcome [18] 0 0
Duration of MRD-negativity
Timepoint [18] 0 0
Up to 5 years
Secondary outcome [19] 0 0
Change in physical functioning as measured by European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C) 30
Timepoint [19] 0 0
Up to 5 years
Secondary outcome [20] 0 0
Change in patient reported outcomes, as measured by EORTC QLQ-C30
Timepoint [20] 0 0
Up to 5 years
Secondary outcome [21] 0 0
Change in patient reported outcomes, as measured by Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS)
Timepoint [21] 0 0
Up to 5 years
Secondary outcome [22] 0 0
Change in patient reported outcomes, as measured by Patient Global Impression of Severity (PGIS)
Timepoint [22] 0 0
Up to 5 years
Secondary outcome [23] 0 0
Change in patient reported outcomes, as measured by Patient Global Impression of Change (PGIC)
Timepoint [23] 0 0
Up to 5 years
Secondary outcome [24] 0 0
Change in patient reported outcomes, as measured by EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)
Timepoint [24] 0 0
Up to 5 years
Secondary outcome [25] 0 0
Change in score of the Functional Assessment of Cancer Therapy-General (FACT-G ) GP5 item
Timepoint [25] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
KEY

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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 3
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
13/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
18/09/2028
Actual
Sample size
Target
904
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [3] 0 0
Icon Cancer Centre - Auchenflower
Recruitment hospital [4] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [5] 0 0
Epworth Freemasons - East Melbourne
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
4066 - Auchenflower
Recruitment postcode(s) [4] 0 0
4217 - Benowa
Recruitment postcode(s) [5] 0 0
3121 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Austria
State/province [13] 0 0
Styria
Country [14] 0 0
Austria
State/province [14] 0 0
Upper Austria
Country [15] 0 0
Austria
State/province [15] 0 0
Graz
Country [16] 0 0
Austria
State/province [16] 0 0
Vienna
Country [17] 0 0
Austria
State/province [17] 0 0
Wels
Country [18] 0 0
Belgium
State/province [18] 0 0
Oost-Vlaanderen
Country [19] 0 0
Belgium
State/province [19] 0 0
West Flanders
Country [20] 0 0
Belgium
State/province [20] 0 0
Brussels
Country [21] 0 0
Belgium
State/province [21] 0 0
Herentals
Country [22] 0 0
Belgium
State/province [22] 0 0
Verviers
Country [23] 0 0
Chile
State/province [23] 0 0
Las Condes
Country [24] 0 0
Chile
State/province [24] 0 0
Region Metropolitana
Country [25] 0 0
Chile
State/province [25] 0 0
Región Metropolitana
Country [26] 0 0
Czechia
State/province [26] 0 0
Hradec Kralove 5
Country [27] 0 0
Czechia
State/province [27] 0 0
Prague
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Czechia
State/province [28] 0 0
Praha
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France
State/province [29] 0 0
Bretagne
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France
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Centre Val De Loire
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France
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Gironde
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France
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Nord
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France
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Nouvelle Aquitaine
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France
State/province [34] 0 0
Nouvelle-Aquitaine
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France
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Paris
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France
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Savoie
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France
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Angers
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France
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Metz Tessy
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France
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Nantes
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France
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Nimes
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France
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Saint-Etienne
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France
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Île De France
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Germany
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North Rhine-Westphalia
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Germany
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Sachsen
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Germany
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Dresden
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Germany
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Kiel
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Germany
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Mainz
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Germany
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Oder
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Ireland
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Dublin
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Israel
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Ashdod
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Nahariya
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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Forli-Cesena
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Italy
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Milano
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Italy
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Modena
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Monza
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Italy
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Napoli
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Italy
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Novara
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Italy
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Pavia
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Perugia
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Italy
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Ravenna
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Italy
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Udine
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Korea, Republic of
State/province [66] 0 0
Gyeonggi-do
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Korea, Republic of
State/province [67] 0 0
Busan
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Korea, Republic of
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Daegu
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Malaysia
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Pahang
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Malaysia
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Sabah
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Malaysia
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Selangor
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Malaysia
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W.Persekutuan
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Malaysia
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Ampang
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Poland
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Malopolskie
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Pomerania
Country [78] 0 0
Poland
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Wielkopolska
Country [79] 0 0
Poland
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Bydgoszcz
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Poland
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Walbrzych
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Singapore
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Singapore
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Spain
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A Coruna
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Spain
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Asturias
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Spain
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Balearic Islands
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Spain
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Barcelona
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Spain
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Cantabria
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Spain
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Madrid
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Spain
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Granada
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Spain
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Sevilla
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Spain
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Toledo
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Spain
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Valencia
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Taiwan
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Chiayi
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Taiwan
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Changhua City
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Taiwan
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New Taipei City
Country [95] 0 0
Taiwan
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Taipei
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Taiwan
State/province [96] 0 0
Taoyuan
Country [97] 0 0
Thailand
State/province [97] 0 0
Krung Thep Maha Nakhon [Bangko]
Country [98] 0 0
Thailand
State/province [98] 0 0
Bangkok
Country [99] 0 0
Thailand
State/province [99] 0 0
Chiang Mai
Country [100] 0 0
Thailand
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Khon Kaen
Country [101] 0 0
Turkey
State/province [101] 0 0
Ankara
Country [102] 0 0
Turkey
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Mersin
Country [103] 0 0
Turkey
State/province [103] 0 0
Suleymanpasa
Country [104] 0 0
Turkey
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Besevler
Country [105] 0 0
Turkey
State/province [105] 0 0
Istanbul
Country [106] 0 0
Turkey
State/province [106] 0 0
Izmir
Country [107] 0 0
Turkey
State/province [107] 0 0
Sakarya
Country [108] 0 0
Turkey
State/province [108] 0 0
Samsun
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Aberdeen
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Uxbridge

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

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT06091865
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/study/NCT06091865