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

NCT ID: NCT02290951

Last Updated: 2025-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-09
• Study Completion Date: 2025-08-21

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A

DLBCL post CAR-T

Group Type: EXPERIMENTAL

Odronextamab multiple dose levels

Intervention Type: DRUG

Administered by intravenous (IV) infusion

1N Part B

FL

Group Type: EXPERIMENTAL

Odronextamab multiple dose levels

Intervention Type: DRUG

Administered by subcutaneous (SC) injection

2N Part B

DLBCL

Group Type: EXPERIMENTAL

Odronextamab multiple dose levels

Intervention Type: DRUG

Administered by subcutaneous (SC) injection

Interventions

Odronextamab multiple dose levels

Administered by intravenous (IV) infusion

Intervention Type: DRUG

Odronextamab multiple dose levels

Administered by subcutaneous (SC) injection

Intervention Type: DRUG

Other Intervention Names

REGN1979; REGN1979

Eligibility Criteria

Inclusion Criteria

1. 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

2. 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.

• For the inclusion in the disease-specific expansion cohort enrolling DLBCL patients after failure of CAR-T therapy, the patient must have recovered from the toxicities of the lymphodepletion therapy and CAR-T infusion.
• For inclusion in Part B, patients must have FL grade 1-3a or DLBCL (with or without prior CAR-T) per the criteria above, and:
• 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

3. 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.

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

5. Life expectancy of at least 6 months

6. Adequate bone marrow function as described in the protocol

7. Adequate organ function as described in the protocol

8. 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.

9. Willing and able to comply with clinic visits and study-related procedures

10. Provide signed informed consent or legally acceptable representative

Exclusion Criteria

1. Primary central nervous system (CNS) lymphoma or known or suspected CNS involvement by non-primary CNS NHL

2. 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

3. Standard anti-lymphoma chemotherapy (non-biologic) or radiotherapy within 28 days prior to first administration of study drug

4. 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)].

1. 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.

2. 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.

5. Patients who have received a live vaccination within 28 days of first dose of study treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

University of California, Irvine

Orange, California, United States

Stanford University

Stanford, California, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

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

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

Centre Henri Becquerel

Rouen, Haute-Normandie, France

CHU Hôpital Lyon Sud

Lyon, , France

Institut Gustave Roussy

Villejuif, Île-de-France Region, France

Universitatsklinikum Wurzburg

Würzburg, Bavaria, Germany

Meir Medical Center

Kfar Saba, Central District, Israel

The Chaim Sheba Medical Center

Tel-Hashomer, Central District, Israel

Hadassah Medical Center

Jerusalem, Jerusalem, Israel

Assuta Ashdod University Hospital

Ashdod, Southern District, Israel

Rambam Health Care Campus - Hematology and Bone Marrow Transplantation Institute

Haifa, , Israel

Lady Davis Carmel Medical Center

Haifa, , Israel

Royal Cornwall Hospitals NHS Trust

Truro, Cornwall, United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

United States; France; Germany; Israel; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39786390 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35366963 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34997701 (View on PubMed)

Other Identifiers

2015-004491-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-514938-20-00

Identifier Type: CTIS

Identifier Source: secondary_id

R1979-HM-1333

Identifier Type: -

Identifier Source: org_study_id