A trial to learn if odronextamab combined with lenalidomide is safe and works better than rituximab combined with lenalidomide in adult participants with follicular lymphoma and marginal zone lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

8 Jan 2024 → ongoing

Decision date (initial)

2023-09-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Regeneron Pharmaceuticals, Inc.

External identifiers

EU CT number

2022-503092-28-00

ClinicalTrials.gov

NCT06149286

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

Part 1 (Safety Run-In)
Assess the safety, tolerability, and dose-limiting toxicities (DLTs) of odronextamab in combination with lenalidomide in participants with relapsed/refractory (R/R) indolent lymphoma (FL and MZL).

Part 2 (Randomized Phase)
To compare the efficacy of odronextamab in combination with lenalidomide versus rituximab in combination with lenalidomide (R2) in participants with R/R FL and subsequently in participants with indolent lymphoma (combined R/R FL and marginal zone lymphoma (MZL)) as measured by progression-free survival (PFS) per independent central review.

Secondary objectives 10

1. Part 1: To characterize the pharmacokinetics (PK) of odronextamab in participants with R/R indolent lymphoma.
2. Part 1: To assess the immunogenicity of odronextamab
3. Part 1:To evaluate the preliminary anti-tumor activity of odronextamab in participants with R/R indolent lymphoma
4. Part 2: To compare efficacy of odronextamab in combination with lenalidomide versus R2 as measured per independent central review by the following endpoints: Complete response (CR), Best overall response (BOR), Overall survival (OS)
5. Part 2: To assess additional measures of efficacy of odronextamab in combination with lenalidomide versus R2
6. Part 2: To evaluate safety and tolerability of odronextamab in combination with lenalidomide versus R2 - from secondary objectives
7. Part 2: To evaluate the PK of odronextamab
8. Part 2: To assess the immunogenicity of odronextamab.
9. Part 2: To evaluate the impact of odronextamab in combination with lenalidomide versus R2 on patient-reported outcomes including health-related quality-of-life, functioning symptoms and general health status.
10. Part 2: To evaluate patient reported overall impact of treatment toxicity for odronextamab in combination with lenalidomide versus R2

Conditions and MedDRA coding

Relapsed/Refractory Follicular Lymphoma

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Local histologic confirmation of FL grade 1-3a or MZL (nodal, splenic, or extra nodal MZL) as assessed by the investigator, as described in the protocol.
2. Have refractory disease or relapsed after at least one prior line (with a duration of at least 2 cycles) of systemic chemo-immunotherapy or immunotherapy. Prior systemic therapy should have included at least one anti-cluster of differentiation 20 (CD20) monoclonal antibody and participant should meet indication for treatment as described in the protocol.
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, as described in the protocol.
6. All study participants must: a. Have an understanding that lenalidomide could have a potential teratogenic risk. b. Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of lenalidomide. c. Agree not to share study medication with another person. d. Agree to be counseled about pregnancy precautions and risk of fetal exposure associated with lenalidomide.
7. Note: Other protocol-defined Inclusion criteria apply

Exclusion criteria 8

1. Primary central nervous system (CNS) lymphoma or known involvement (either current or prior history of CNS involvement) by non-primary CNS Non-Hodgkin lymphoma (NHL), as described in the protocol.
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, as described in the protocol.
7. Active infection as defined in the protocol.
8. Note: Other protocol-defined Exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1: Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with lenalidomide
2. Part 1: Incidence of treatment emergent adverse events (TEAEs) for odronextamab in combination with lenalidomide
3. Part 1: Severity of TEAEs for odronextamab in combination with lenalidomide
4. Part 2: Progression-free survival (PFS) as assessed by independent central review (ICR) in participants with R/R FL and participants with indolent lymphoma (FL and MZL)

Secondary endpoints 22

1. Part 1 & 2: Odronextamab concentrations in serum
2. Part 1 & 2: Incidence of anti-drug antibodies (ADA) to odronextamab over the study duration
3. Part 1 & 2: Titer of ADAs to odronextamab over the study duration
4. Part 1 & 2: Incidence of neutralizing antibodies (NAbs) to odronextamab over the study duration
5. Part 1 & 2: Best overall response (BOR) as assessed by investigator review
6. Part 1 & 2: Duration of response (DOR) as assessed by investigator review
7. Part 1 & 2: PFS as assessed by investigator review
8. Part 2: Complete response (CR) as assessed by ICR
9. Part 2: BOR as assessed by ICR
10. Part 2: Overall survival (OS)
11. Part 2: Event free survival (EFS) as assessed by ICR
12. Part 2: EFS as assessed by local investigator review
13. Part 2: DOR as assessed by ICR
14. Part 2: Time to next anti-lymphoma treatment (TTNT)
15. Part 2: Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2
16. Part 2: Severity of TEAEs for odronextamab in combination with lenalidomide versus R2
17. Part 2: Overall change in patient reported outcomes (PROs) as measured by scores of European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQC30)
18. Part 2: Overall change in PROs as measured by scores of Functional Assessment of Cancer Therapy–Lymphoma Subscale (FACT-LymS)
19. Part 2: Overall change in PROs as measured by scores of Patient Global Impression on Severity (PGIS)
20. Part 2: Overall change in PROs as measured by scores of Patient Global Impression on Change (PGIC)
21. Part 2: Overall change in PROs as measured by scores of EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)
22. Part 2: Overall change in score of the global population item 5 (GP5) items of the Functional Assessment of Cancer Therapy–General (FACT-G) questionnaire

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Head EU Regulatory Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Head EU Regulatory Affairs

Third parties 9

Locations

8 EU/EEA countries · 88 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 300 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications