Odronextamab for Relapsed and Refractory Large B-cell Lymphomas Before CAR-T

NCT06784726 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1124641NCI-2024-10534FHIRB0020747
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests the effectiveness of odronextamab given before chimeric antigen receptor T (CAR-T) cell therapy (bridging therapy) in patients with large B-cell lymphomas that have come back after a period of improvement (relapsed) or that have not responded to previous treatment (refractory). Odronextamab is a bispecific antibody that can bind to two different antigens at the same time. Odronextamab binds to CD3, a T-cell surface antigen, and CD20 (a tumor-associated antigen that is expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell cancers) and may interfere with the ability of cancer cells to grow and spread. Bridging therapy has been used to maintain disease control and to increase the chance of successful receipt of CAR-T cell therapy. However, bridging therapy is typically given after leukapheresis, which does not help prevent disease progression between the decision for CAR-T cell therapy and leukapheresis. Giving odronextamab as bridging therapy before leukapheresis may delay disease progression to allow leukapheresis and increase the likelihood of successful CAR-T cell therapy in patients with relapsed or refractory large B-cell lymphomas.

Conditions

Recurrent High Grade B-Cell Lymphoma; Recurrent Primary Mediastinal Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Refractory Grade 3b Follicular Lymphoma; Refractory High Grade B-Cell Lymphoma; Refractory Primary Mediastinal Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Recurrent Grade 3b Follicular Lymphoma; Recurrent Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma; Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Failure to undergo leukapheresis

  Will include failures due to disease progression or adverse events (AEs) due to odronextamab (Odron), or requirement of other lymphoma-directed therapy for bridging before leukapheresis due to lack of response. Will report the total number and percentage with 95% confidence interval (CI).

  Up to 5 years

Secondary Outcomes (6)

• Receipt of chimeric antigen receptor T-cell therapy (CAR-T)

  Up to 5 years

• Overall response rate (ORR) following bridging prior to CAR-T infusion

  Up to 5 years

• Progression free survival (PFS) following CAR-T infusion

  Up to 2 years

• CR rate

  At 1 month after CAR-T

• PFS in patients who achieve CR after 2 cycles of Odron, choose to opt out of CAR-T, and receive up to a total of 12 months of Odron

  Up to 5 years

Study Arms (1)

Treatment (odronextamab)

EXPERIMENTAL

Patients receive odronextamab IV based on the following schedules: * Step-up dosing during cycle 1: 0.2 mg on C1D1, 0.5 mg on C1D2, 2 mg on C1D8 and C1D9, respectively, and 10 mg on C1D15 and C1D16, respectively (0.7/4/20 regimen). * Dosing during cycles 2-4: Odron will be given at 160 mg weekly. * Once every other week at 320 mg of remaining cycles. Please see the Detailed Description for additional information.

Biological: Odronextamab; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Biological: Chimeric Antigen Receptor T-Cell Therapy; Procedure: Computed Tomography; Procedure: Leukapheresis; Procedure: Lumbar Puncture; Procedure: Positron Emission Tomography; Other: Questionnaire Administration; Procedure: Biopsy Procedure

Interventions

Biopsy Procedure PROCEDURE

Undergo tissue biopsy

Also known as: Bx

Treatment (odronextamab)

Odronextamab BIOLOGICAL

Given IV

Also known as: REGN1979, Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody REGN1979, WHO 11035

Treatment (odronextamab)

Biospecimen Collection PROCEDURE

Undergo collection of blood and oral or rectal swab samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (odronextamab)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (odronextamab)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (odronextamab)

Chimeric Antigen Receptor T-Cell Therapy BIOLOGICAL

Undergo CAR-T cell therapy

Also known as: CAR T Infusion, CAR T Therapy, CAR T-cell Therapy, Chimeric Antigen Receptor T-cell Infusion

Treatment (odronextamab)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (odronextamab)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Treatment (odronextamab)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (odronextamab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (odronextamab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (odronextamab)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed large B cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, DLBCL arising from indolent lymphoma, follicular lymphoma (FL) grade 3B
• Measurable disease, defined as at least one measurable lesion ≥ 15 mm on PET, CT, or magnetic resonance imaging (MRI) within one month of screening, according to the International Working Group consensus response evaluation criteria in lymphoma
• Prior frontline therapy for large B cell lymphoma must have failed the patient, and criteria must be met for receiving commercial axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), or tisagenlecleucel (tisa-cel) per Food and Drug Administration (FDA) label
• Age ≥ 18 years
• Capable of understanding and providing a written informed consent
• Prior treatment with an anti-CD20 antibody therapy
• Eastern Cooperative Oncology Group performance status of 0-1; we allow enrollment of patients with a performance status of 2 if it is attributed to lymphoma per discretion of the treating physician or principal investigator (PI)
• Creatinine clearance ≥ 45 mL/min calculated by Cockcroft-Gault equation
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN), except in patients with Gilbert's syndrome
• Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x the ULN
• Adequate pulmonary function, defined as ≤ grade 1 dyspnea and oxygen saturation (SpO2) ≥ 92% on room air
• Adequate cardiac function, defined as left ventricular ejection fraction ≥ 50% and without evidence for pericardial effusion
• Platelet count ≥ 75 x 10\^9 /L
• Hemoglobin (Hg) level ≥ 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1 x 10\^9 /L

You may not qualify if:

• Detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases. Patients with a history of secondary central nervous system (CNS) lymphoma may be eligible provided that there has been no evidence of CNS disease from lymphoma for at least 3 months at the time of screening
• History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
• Standard anti-neoplastic chemotherapy (non-biologic) within 5-times the half-life or within 2 weeks, whichever is shorter, prior to first administration of study drug
• Standard radiotherapy within 2 weeks of first administration of study drug
• Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy, unless all the following are met: disease responded to prior bispecific therapy (CR or PR per Lugano criteria) and did not experience disease progression within 12 months of the last dose of prior bispecific therapy, and the tumor must still express CD20 (CD20 examination per standard of care \[SOC\])
• Allogeneic stem cell transplantation
• Any CAR-T cell therapy
• Patients may not be receiving other investigational agents
• Treatment with rituximab, alemtuzumab, or other investigational or commercial biologic agent within 2 weeks prior to first administration of study drug
• Immunosuppressive therapy (other than biologic) within 2 weeks of first administration of study drug
• Treatment with an investigational non-biologic agent within 2 weeks of first administration of study drug
• History of allergic reactions attributed to compounds of similar chemical or biologic composition of study drug
• History of hypersensitivity to any compound in the tetracycline antibiotics group
• Concurrent active malignancy for which the patient is receiving systemic treatment, unless approved by PI
• Known active and uncontrolled bacterial, viral, fungal, mycobacterial, or other infection

Sponsors & Collaborators

• University of Washington: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Specimen Handling; Biopsy; Immunotherapy, Adoptive; Leukapheresis; Spinal Puncture; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Diagnostic Techniques, Neurological; Punctures; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Mengyang Di, MD, PhD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mengyang Di, MD, PhD

CONTACT

206-606-2509; mydi@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 20, 2025
• Study Start: September 4, 2025
• Primary Completion (Estimated): April 10, 2028
• Study Completion (Estimated): April 11, 2033
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)