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

Phase 2

Recruiting

• Conditions: B-cell non-Hodgkin lymphoma (NHL)

• Registration Number: 2024-511747-25-00
• Lead Sponsor: Regeneron Pharmaceuticals Inc.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-05-28
• Last Update Posted: 2025-04-04

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 225

Inclusion Criteria

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

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

Other protocol-defined inclusion criteria apply

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

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 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.

Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment

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

Exclusion Criteria

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).

Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy

Other protocol-defined exclusion criteria apply

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.

History of allogeneic stem cell transplantation

Criterion removed

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

History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded

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.

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

Known hypersensitivity to both allopurinol and rasburicase

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.		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 Outcome Measures

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

Trial Locations

Locations (38)

Universitaetsklinikum Halle (Saale) AöR; 🇩🇪 Halle Saale, Germany

Kliniken Ostalb gemeinnuetzige kommunale Anstalt des oeffentlichen Rechts; 🇩🇪 Mutlangen, Germany

Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH; 🇩🇪 Villingen-Schwenningen, Germany

Azienda Unita Sanitaria Locale Della Romagna; 🇮🇹 Ravenna, Italy

Azienda USL IRCCS Di Reggio Emilia; 🇮🇹 Reggio Emilia, Italy

Alma Mater Studiorum Universita Di Bologna; 🇮🇹 Bologna, Italy

Azienda Ospedaliero-Universitaria Maggiore Della Carita; 🇮🇹 Novara, Italy

ASST Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milan, Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico; 🇮🇹 Milan, Italy

Hospital Santa Maria Della Misericordia; 🇮🇹 Perugia, Italy

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Universitaetsklinikum Halle (Saale) AöR

🇩🇪Halle Saale, Germany

Thomas Weber

Site contact

+493455574959

thomas.weber@uk-halle.de