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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06149286




Registration number
NCT06149286
Ethics application status
Date submitted
20/11/2023
Date registered
28/11/2023
Date last updated
11/06/2024

Titles & IDs
Public title
A Trial to Learn if Odronextamab Combined With Lenalidomide is Safe and Works Better Than Rituximab Combined With Lenalidomide in Participants With Follicular Lymphoma and Marginal Zone Lymphoma
Scientific title
A Phase 3, Open Label, Randomized Study to Compare the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Combination With Lenalidomide Versus Rituximab in Combination With Lenalidomide Therapy in Relapsed/Refractory Participants With Follicular Lymphoma and Marginal Zone Lymphoma (OLYMPIA-5)
Secondary ID [1] 0 0
2022-503092-28-00
Secondary ID [2] 0 0
R1979-ONC-22102
Universal Trial Number (UTN)
Trial acronym
OLYMPIA-5
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Follicular Lymphoma 0 0
Marginal Zone Lymphoma (MZL) 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 - Lenalidomide
Treatment: Drugs - Rituximab

Experimental: Odronextamab+Lenalidomide - In part 1 (safety run-in), participants with R/R indolent lymphoma (FL and ML), will receive odronextamab in combination with lenalidomide.

In part 2, 1:1 randomized participants with indolent lymphoma (FL/MZL), will receive odronextamab in combination with lenalidomide.

Experimental: Rituximab+Lenalidomide - In part 2 only, 1:1 randomized participants with R/R lymphoma (FL and ML), will receive rituximab in combination with lenalidomide (R2) followed by lenalidomide monotherapy.


Treatment: Drugs: Odronextamab
Administered by intravenous (IV) infusion

Treatment: Drugs: Lenalidomide
Administered orally (PO)

Treatment: Drugs: Rituximab
Administered by IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with lenalidomide
Timepoint [1] 0 0
Up to 35 days
Primary outcome [2] 0 0
Incidence of treatment emergent adverse events (TEAEs) for odronextamab in combination with lenalidomide
Timepoint [2] 0 0
Up to 2 years
Primary outcome [3] 0 0
Severity of TEAEs for odronextamab in combination with lenalidomide
Timepoint [3] 0 0
Up to 2 years
Primary outcome [4] 0 0
Progression-free survival (PFS) as assessed by independent central review (ICR) in participants with R/R FL and participants with indolent lymphoma
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Odronextamab concentrations in serum
Timepoint [1] 0 0
Up to 30 months
Secondary outcome [2] 0 0
Incidence of anti-odronextamab antibodies (ADA) to odronextamab over time
Timepoint [2] 0 0
Up to 30 months
Secondary outcome [3] 0 0
Titer of ADAs to odronextamab over time
Timepoint [3] 0 0
Up to 30 months
Secondary outcome [4] 0 0
Incidence of neutralizing antibodies (NAbs) to odronextamab over time
Timepoint [4] 0 0
Up to 30 months
Secondary outcome [5] 0 0
Best overall response (BOR) as assessed by investigator review
Timepoint [5] 0 0
Up to 30 months
Secondary outcome [6] 0 0
Duration of response (DOR) as assessed by investigator review
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
PFS as assessed by investigator review
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Complete response (CR) as assessed by ICR
Timepoint [8] 0 0
Up to 30 months
Secondary outcome [9] 0 0
BOR as assessed by ICR
Timepoint [9] 0 0
Up to 30 months
Secondary outcome [10] 0 0
Overall survival (OS)
Timepoint [10] 0 0
Up to 5 years
Secondary outcome [11] 0 0
Event free survival (EFS) as assessed by ICR
Timepoint [11] 0 0
Up to 5 years
Secondary outcome [12] 0 0
EFS as assessed by local investigator review
Timepoint [12] 0 0
Up to 5 years
Secondary outcome [13] 0 0
DOR as assessed by ICR
Timepoint [13] 0 0
Up to 5 years
Secondary outcome [14] 0 0
Time to next anti-lymphoma treatment (TTNT)
Timepoint [14] 0 0
Up to 5 years
Secondary outcome [15] 0 0
Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2
Timepoint [15] 0 0
Up to 2 years
Secondary outcome [16] 0 0
Severity of TEAEs for odronextamab in combination with lenalidomide versus R2
Timepoint [16] 0 0
Up to 2 years
Secondary outcome [17] 0 0
Overall change from baseline in patient reported outcomes (PROs) as measured by scores of European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQC30)
Timepoint [17] 0 0
Up to 5 years
Secondary outcome [18] 0 0
Overall change from baseline in PROs as measured by scores of Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)
Timepoint [18] 0 0
Up to 5 years
Secondary outcome [19] 0 0
Overall change from baseline in PROs as measured by scores of Patient Global Impression on Severity (PGIS)
Timepoint [19] 0 0
Up to 5 years
Secondary outcome [20] 0 0
Overall change from baseline in PROs as measured by scores of Patient Global Impression on Change (PGIC)
Timepoint [20] 0 0
Up to 5 years
Secondary outcome [21] 0 0
Overall change from baseline in PROs as measured by scores of EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)
Timepoint [21] 0 0
Up to 5 years
Secondary outcome [22] 0 0
Overall change from first assessment to end of treatment in score of the global population item 5 (GP5) items of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire
Timepoint [22] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
Key

1. Local histologic confirmation of FL grade 1-3a or MZL (nodal, splenic, or extra nodal MZL) as assessed by the investigator.
2. Must have refractory disease or relapsed after at least 2 cycles of prior systemic chemo-immunotherapy or immunotherapy. Prior systemic therapy should have included at least one anti-cluster of differentiation 20 (CD20) monoclonal antibody and patient should meet indication for treatment.
3. Have measurable disease on cross sectional imaging documented by diagnostic computed tomography [CT], or magnetic resonance imaging [MRI] imaging, as described in the protocol.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Adequate hematologic and organ function.

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 (either current or prior history of CNS involvement) by non-primary CNS NHL.
2. Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma, or any histology other than FL grade 1-3a or MZL.
3. History of or current relevant CNS pathology, as described in the protocol.
4. 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 treated with hormone therapy or local radiotherapy (ie, pellets), cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated.
5. 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.
6. Allergy/hypersensitivity to study drugs or excipients.
7. Active infection as defined 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
28/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/10/2029
Actual
Sample size
Target
470
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
Epworth Freemasons Hospital - East Melbourne
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
3121 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Indiana
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Wisconsin
Country [4] 0 0
Belgium
State/province [4] 0 0
Oost-Vlaanderen
Country [5] 0 0
Belgium
State/province [5] 0 0
West Flanders
Country [6] 0 0
Belgium
State/province [6] 0 0
Brussels
Country [7] 0 0
Belgium
State/province [7] 0 0
Yvoir
Country [8] 0 0
Czechia
State/province [8] 0 0
Hradec Kralove 5
Country [9] 0 0
Czechia
State/province [9] 0 0
Prague
Country [10] 0 0
France
State/province [10] 0 0
Cedex 10
Country [11] 0 0
France
State/province [11] 0 0
Centre-Val De Loire
Country [12] 0 0
France
State/province [12] 0 0
Gironde
Country [13] 0 0
France
State/province [13] 0 0
Ile De France
Country [14] 0 0
France
State/province [14] 0 0
Nord
Country [15] 0 0
France
State/province [15] 0 0
Normandie
Country [16] 0 0
France
State/province [16] 0 0
Savoie
Country [17] 0 0
France
State/province [17] 0 0
Nantes
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
France
State/province [19] 0 0
Rennes
Country [20] 0 0
France
State/province [20] 0 0
Île De France
Country [21] 0 0
France
State/province [21] 0 0
Île-de-France
Country [22] 0 0
Italy
State/province [22] 0 0
Forli-Cesena
Country [23] 0 0
Italy
State/province [23] 0 0
Monza E Brianza
Country [24] 0 0
Italy
State/province [24] 0 0
Province Of Pordenone
Country [25] 0 0
Italy
State/province [25] 0 0
Torino
Country [26] 0 0
Italy
State/province [26] 0 0
Bologna
Country [27] 0 0
Italy
State/province [27] 0 0
Brescia
Country [28] 0 0
Italy
State/province [28] 0 0
Genova
Country [29] 0 0
Italy
State/province [29] 0 0
Milano
Country [30] 0 0
Italy
State/province [30] 0 0
Napoli
Country [31] 0 0
Italy
State/province [31] 0 0
Novara
Country [32] 0 0
Italy
State/province [32] 0 0
Ravenna
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Gyeonggi-do
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul Teugbyeolsi
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Busan
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Daegu
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Suwon
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Ulsan
Country [40] 0 0
Malaysia
State/province [40] 0 0
Johor
Country [41] 0 0
Malaysia
State/province [41] 0 0
Sabah
Country [42] 0 0
Malaysia
State/province [42] 0 0
Selangor
Country [43] 0 0
Poland
State/province [43] 0 0
Malopolska
Country [44] 0 0
Poland
State/province [44] 0 0
Wielkopolska
Country [45] 0 0
Poland
State/province [45] 0 0
Katowice
Country [46] 0 0
Spain
State/province [46] 0 0
A Coruña
Country [47] 0 0
Spain
State/province [47] 0 0
Balearic Islands
Country [48] 0 0
Spain
State/province [48] 0 0
Cantabria
Country [49] 0 0
Spain
State/province [49] 0 0
Madrid
Country [50] 0 0
Spain
State/province [50] 0 0
Barcelona
Country [51] 0 0
Spain
State/province [51] 0 0
Granada
Country [52] 0 0
Spain
State/province [52] 0 0
Salamanca
Country [53] 0 0
Spain
State/province [53] 0 0
Seville
Country [54] 0 0
Spain
State/province [54] 0 0
Valencia
Country [55] 0 0
Taiwan
State/province [55] 0 0
Chiayi City
Country [56] 0 0
Taiwan
State/province [56] 0 0
New Taipei City
Country [57] 0 0
Taiwan
State/province [57] 0 0
Taipei City
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taipei
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taoyuan City
Country [60] 0 0
Thailand
State/province [60] 0 0
Krung Thep Maha Nakhon [Bangko]
Country [61] 0 0
Thailand
State/province [61] 0 0
Bangkok
Country [62] 0 0
Thailand
State/province [62] 0 0
Chiang Mai
Country [63] 0 0
Turkey
State/province [63] 0 0
Ankara
Country [64] 0 0
Turkey
State/province [64] 0 0
Suleymanpasa
Country [65] 0 0
Turkey
State/province [65] 0 0
Izmir
Country [66] 0 0
Turkey
State/province [66] 0 0
Sakarya
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Devon
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Dorset

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. The study is focused on patients who have one of two types of cancer: follicular lymphoma (FL) or marginal zone lymphoma (MZL) that has come back after treatment (called "relapsed"), or did not respond to treatment (called "refractory"). FL and MZL are subtypes of Non-Hodgkin 's lymphoma (NHL).

This study will be made up of two parts (Part 1 not randomized, Part 2 randomized - controlled). The aim of Part 1 of the study is to see how safe and tolerable the study drug is when used in combination with lenalidomide, in participants with FL or MZL, and to determine the dose of the study drug to be used in Part 2 of this study. This combination is considered "first-in-human" as it has not been tested as a combination treatment in humans before. The aim of Part 2, of the study is to assess how the combination of odronextamab and lenalidomide works compared to the combination of rituximab and lenalidomide, (the current standard-of-care treatment for FL and/or MZL). 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 in combination with lenalidomide
* How much study drug is in your 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 your quality-of-life and ability to complete routine daily activities
Trial website
https://clinicaltrials.gov/study/NCT06149286
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
clinicaltrials@regeneron.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06149286