A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Adult Patients With B-cell Non-Hodgkin Lymphoma Who Have Been Previously Treated with Other Cancer Therapies

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

23 Dec 2019 → ongoing

Decision date (initial)

2024-05-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceuticals Inc

External identifiers

EU CT number

2024-511747-25-00

EudraCT number

2017-002139-41

ClinicalTrials.gov

NCT03888105

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Dose response, Pharmacokinetic, Pharmacodynamic

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 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 that has relapsed after or is refractory to at least 2 prior lines of systemic therapy including an anti-CD20 antibody and an alkylating agent

- In patients with diffuse large B-cell lymphoma (DLBCL) that has relapsed after or is refractory to at least 2 prior lines of systemic therapy including an anti-CD20 antibody and an alkylating agent

- In patients with mantle cell lymphoma (MCL) who have relapsed or refractory disease to at least one prior line of systemic therapy and had prior Bruton’s tyrosine kinase (BTK) inhibitor treatment.

- In patients with marginal zone lymphoma (MZL) that has relapsed after or is refractory to at least 2 prior lines of systemic therapy

- In patients with other B-NHL subtypes that has relapsed after or is refractory to at least 2 prior lines of systemic therapy

Secondary objectives 10

1. 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
2. To assess the anti-tumor activity of single agent odronextamab in each of 5 disease-specific cohorts, as measured by complete response (CR) rate according to the Lugano Classification and as assessed local by local investigator evaluation and independent central review
3. To assess the anti-tumor activity of single agent odronextamab in each of 5 disease-specific cohorts, as measured by progression-free survival (PFS) according to Lugano Classification and as assessed by independent central review and local investigator evaluation
4. To assess the anti-tumor activity of single agent odronextamab in each of 5 disease-specific cohorts, as measured by overall survival (OS)
5. To assess the anti-tumor activity of single agent odronextamab in each of 5 disease-specific cohorts, as measured by duration of response (DOR) according to Lugano Classification and as assessed by independent central review and local investigator evaluation
6. To assess the anti-tumor activity of single agent odronextamab in each of 5 disease-specific cohorts, as measured by disease control rate (DCR) according to Lugano Classification and as assessed by independent central review and local investigator evaluation
7. To evaluate the safety and tolerability of odronextamab
8. To assess the pharmacokinetics (PK) of Odronextamab
9. To assess the immunogenicity of Odronextamab
10. 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)

Conditions and MedDRA coding

B-cell non-Hodgkin lymphoma (NHL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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
2. Adequate bone marrow, hepatic, and renal function as defined in the protocol
3. Disease-specific cohorts: Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment. FL grade 1-3a cohort: Patients with FL grade 1-3a that has relapsed after or is refractory to at least 2 prior lines of systemic therapy, as defined in the protocol
4. 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
5. MCL after BTK inhibitor therapy cohort: Patients with MCL who have relapsed or refractory disease to at least one prior line of systemic therapy and had prior treatment with a BTK inhibitor.
6. MZL cohort: Patients with MZL that have relapsed or is refractory to at least 2 prior lines of systemic therapy.
7. 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.
8. Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment
9. Measurable disease on cross sectional imaging as defined in the protocol documented by diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI)
10. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
11. Other protocol-defined inclusion criteria apply

Exclusion criteria 11

1. 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).
2. 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.
3. History of allogeneic stem cell transplantation
4. Criterion removed
5. 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
6. History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded
7. 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.
8. 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
9. Known hypersensitivity to both allopurinol and rasburicase
10. Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy
11. Other protocol-defined exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study for each of the 5 disease-specific cohorts is as follows: ORR according to the Lugano Classification of response in malignant lymphoma (Cheson, 2014) and as assessed by independent central review.

Secondary endpoints 11

1. ORR according to the Lugano Classification and as assessed by local investigator evaluation
2. Complete response (CR) rate according to the Lugano Classification and as assessed by local investigator evaluation and independent central review.
3. Progression free survival (PFS) according to the Lugano Classification and as assessed by independent central review and local investigator evaluation
4. Overall survival (OS)
5. Duration of response (DOR) according to the Lugano Classification and as assessed by independent central review and local investigator evaluation
6. Disease control rate (DCR) according to the Lugano Classification and as assessed by independent central review and local investigator evaluation by independent central review and local investigator evaluation
7. Incidence and severity of treatment emergent adverse events (TEAEs)
8. Pharmacokinetics: concentration of odronextamab, incidence of anti-drug antibodies (ADA) to odronextamab over time, incidence of neutralizing antibodies (Nab) to odronextamab over time
9. Changes in scores of patient-reported outcomes as measured by EORTC QLQ-C30
10. Changes in scores of patient-reported outcomes as measured by FACT-Lym
11. Changes in scores of patient-reported outcomes as measured by EQ-5D-3L

Investigational products

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

Test 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 8

Locations

5 EU/EEA countries · 37 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 80 files

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

Application history

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