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 (ELM-2)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: B-cell Non-Hodgkin Lymphoma (B-NHL)

Treatments: Drug: Odronextamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03888105

R1979-ONC-1625

2024-511747-25-00 (Registry Identifier)

2017-002139-41 (EudraCT Number)

Details and patient eligibility

About

This study is researching an investigational drug, odronextamab, in adult patients B-cell non-Hodgkin's lymphoma (B-NHL).

The main purpose of this study is to assess the effectiveness of odronextamab in destroying cancer cells and to learn more about the safety of odronextamab.

The study is looking at several other research questions, including:

• To see if odronextamab works to destroy cancer cells
• Side effects that may be experienced by people taking odronextamab
• How odronextamab works in the body
• How much odronextamab is present in the blood

Enrollment: 576 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

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 (Swerdlow, 2017).

2. 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
   • 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: Patients with MCL who have relapsed or refractory disease to at least one prior line of systemic therapy and had prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor.
   • 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.

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

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

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

Key Exclusion Criteria:

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. 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
5. History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded
6. 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.
7. 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
8. Known hypersensitivity to both allopurinol and rasburicase
9. Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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576 participants in 5 patient groups

FL

Experimental group

Description:

Follicular lymphoma grade 1-3a cohort

Treatment:

Drug: Odronextamab

DLBCL

Experimental group

Description:

Diffuse large B-cell lymphoma cohort

Treatment:

Drug: Odronextamab

MCL

Experimental group

Description:

Mantle Cell Lymphoma cohort

Treatment:

Drug: Odronextamab

MZL

Experimental group

Description:

Marginal Zone Lymphoma cohort

Treatment:

Drug: Odronextamab

Other B-NHL

Experimental group

Description:

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:

Drug: Odronextamab