Study to Investigate the Safety and Tolerability of Odronextamab in Patients With CD20+ B-Cell Malignancies

NCT02290951 | Completed Phase 1 FDA Drug

• 3 other identifiers: R1979-HM-13332015-004491-302024-514938-20-00
• Study Type: interventional
• Target: 200
• Locations: 5 countries
• Sites: 22

Brief Summary

This study has two parts with distinct study objectives and study design. In part A, odronextamab is studied as an intravenous (IV) administration with a dose escalation and a dose expansion phase for B-NHL and CLL. The dose escalation phase for B-NHL and the CLL study are closed at the time of protocol amendment 17. In part B, odronextamab is studied as a subcutaneous (SC) administration with a dose finding and a dose expansion phase for B-NHL.

Conditions

Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia

Keywords

Diffuse large B-cell lymphoma (DLBCL); Follicular lymphoma (FL); Aggressive lymphoma

Outcome Measures

Primary Outcomes (3)

• Safety/overall frequency of adverse events (AEs)

  Part A and B

  Up to 24 months

• Safety/dose limiting toxicities (DLTs)

  Part A and B

  Up to 28 days

• Antitumor activity as measured by the objective response rate (ORR)

  Expansion Cohorts: • Diffuse large B-cell lymphoma (DLBCL) after failure of CAR-T therapy Part A

  Through study completion, an average of 24 months

Secondary Outcomes (10)

• Pharmacokinetics (Concentration of odronextamab)

  Up to 10 months

• Incidence of anti-drug antibodies (ADA) to odronextamab

  Over time; up to approximately 15 months

• Titer of ADA to odronextamab

  Over time; up to approximately 15 months

• Incidence of neutralizing antibodies (NAb) to odronextamab over time

  Over time; Up to approximately 15 months

• Objective response rate (ORR)

  Through study completion, an average of 24 months

Study Arms (3)

Part A

EXPERIMENTAL

DLBCL post CAR-T

Drug: Odronextamab multiple dose levels

1N Part B

EXPERIMENTAL

FL

Drug: Odronextamab multiple dose levels

2N Part B

EXPERIMENTAL

DLBCL

Drug: Odronextamab multiple dose levels

Interventions

Odronextamab multiple dose levels DRUG

Administered by intravenous (IV) infusion

Also known as: REGN1979

Part A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have documented CD20+ B-cell malignancy, with active disease not responsive to prior therapy, for whom no standard of care options exists, and for whom treatment with an anti-CD20 antibody may be appropriate:
• Part A (IV administration) B-NHL confirmed by National Cancer Institute (NCI) working group criteria
• Part B (SC administration): Confirmed diagnosis of B-NHL requiring therapy as defined by WHO classification 2017
• Patients with B-NHL must have had prior treatment with an anti-CD20 antibody therapy. Patients with CLL (Part A only) are not required to have received prior treatment with an anti-CD20 antibody therapy as defined in the protocol.
• Patients with FL grade 1-3a and DLBCL must have received at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent
• All patients must have at least one bi-dimensionally measurable lesion ≥1.5 cm) documented by CT or MRI scan, if CT scan is not feasible.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Life expectancy of at least 6 months
• Adequate bone marrow function as described in the protocol
• Adequate organ function as described in the protocol
• Willingness to undergo mandatory tumor biopsy pretreatment, if in the opinion of the investigator, the patient has an accessible lesion that can be biopsied without significant risk to the patient.
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent or legally acceptable representative

You may not qualify if:

• Primary central nervous system (CNS) lymphoma or known or suspected CNS involvement by non-primary CNS NHL
• History of or current relevant CNS pathology such as
• Epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis, or
• Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI
• Standard anti-lymphoma chemotherapy (non-biologic) or radiotherapy within 28 days prior to first administration of study drug
• Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV) infection \[(as noted by detectable levels on a blood polymerase chain reaction (PCR) assay)\].
• Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus deoxyribonucleic acid (DNA) that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted upon consultation with the physician managing the infection.
• Patients who show detectable levels of CMV at screening will need to be treated with appropriate antiviral therapy and demonstrate at least 2 undetectable levels of CMV by PCR assay (at least 7 days apart) before being re-considered for eligibility.
• Patients who have received a live vaccination within 28 days of first dose of study treatment

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (22)

University of California, Irvine

Orange, California, 92868, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute (Massachusetts General Hospital and Beth Israel)

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Centre Henri Becquerel

Rouen, Haute-Normandie, 76038, France

Location

CHU Hôpital Lyon Sud

Lyon, 69495, France

Location

Institut Gustave Roussy

Villejuif, Île-de-France Region, 94800, France

Location

Universitatsklinikum Wurzburg

Würzburg, Bavaria, 97080, Germany

Location

Meir Medical Center

Kfar Saba, Central District, 44281, Israel

Location

The Chaim Sheba Medical Center

Tel-Hashomer, Central District, 5265601, Israel

Location

Hadassah Medical Center

Jerusalem, Jerusalem, 9112001, Israel

Location

Assuta Ashdod University Hospital

Ashdod, Southern District, 7747629, Israel

Location

Rambam Health Care Campus - Hematology and Bone Marrow Transplantation Institute

Haifa, 3109601, Israel

Location

Lady Davis Carmel Medical Center

Haifa, 3436212, Israel

Location

Royal Cornwall Hospitals NHS Trust

Truro, Cornwall, tr1 3lq, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (3)

• Topp MS, Matasar M, Allan JN, Ansell SM, Barnes JA, Arnason JE, Michot JM, Goldschmidt N, O'Brien SM, Abadi U, Avivi I, Cheng Y, Flink DM, Zhu M, Brouwer-Visser J, Chaudhry A, Mohamed H, Ambati S, Crombie JL. Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: primary analysis of the ELM-1 study. Blood. 2025 Apr 3;145(14):1498-1509. doi: 10.1182/blood.2024027044.

  PMID: 39786390 DERIVED

• Bannerji R, Arnason JE, Advani RH, Brown JR, Allan JN, Ansell SM, Barnes JA, O'Brien SM, Chavez JC, Duell J, Rosenwald A, Crombie JL, Ufkin M, Li J, Zhu M, Ambati SR, Chaudhry A, Lowy I, Topp MS. Odronextamab, a human CD20xCD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Haematol. 2022 May;9(5):e327-e339. doi: 10.1016/S2352-3026(22)00072-2. Epub 2022 Apr 1.

  PMID: 35366963 DERIVED

• Zhu M, Olson K, Kirshner JR, Khaksar Toroghi M, Yan H, Haber L, Meagher C, Flink DM, Ambati SR, Davis JD, DiCioccio AT, Smith EJ, Retter MW. Translational findings for odronextamab: From preclinical research to a first-in-human study in patients with CD20+ B-cell malignancies. Clin Transl Sci. 2022 Apr;15(4):954-966. doi: 10.1111/cts.13212. Epub 2022 Jan 7.

  PMID: 34997701 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2014
• First Posted: November 14, 2014
• Study Start: January 9, 2015
• Primary Completion: August 21, 2025
• Study Completion: August 21, 2025
• Last Updated: October 10, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When Regeneron has: * received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development * made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry) * the legal authority to share the data, and * ensured the ability to protect participant privacy
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

Locations

GB (2); US (10); FR (3); DE (1); IL (6)