Odronextamab as bridging therapy for relapsed or refractory large B‑cell lymphoma before CAR‑T

Odronextamab for Relapsed/Refractory Large B-Cell Lymphomas Before Definitive Lymphoma-Directed Therapies

This trial tests whether giving odronextamab before CAR‑T cell therapy can keep disease under control in adults with relapsed or refractory large B‑cell lymphomas.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Washington (Academic / other)
• Drugs / interventions: odronextamab, rituximab, alemtuzumab, CAR T, CAR-T, chemotherapy, prednisone, chimeric antigen receptor
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT06784726 on ClinicalTrials.gov

What this trial studies

Participants receive intravenous odronextamab with a dose step‑up schedule in cycle 1, then weekly dosing for cycles 2–4 and every other week thereafter for up to 12 months. After two cycles patients undergo leukapheresis followed by lymphodepletion and CAR‑T infusion per standard of care, although patients who achieve a complete response after two cycles may opt out of leukapheresis and continue odronextamab. The protocol includes PET/CT imaging and collection of blood, swabs, tissue, and optional bone marrow or CSF samples to monitor response and safety. Patients are monitored for toxicity for 90 days after treatment and followed for up to five years.

Who should consider this trial

Good fit: Adults (≥18 years) with measurable relapsed or refractory large B‑cell lymphoma who have failed frontline therapy and meet criteria for commercial CAR‑T products are the intended candidates.

Not a fit: Patients without measurable disease, those ineligible for leukapheresis or CAR‑T, or those with contraindications to anti‑CD20 or T‑cell engaging antibodies may not receive benefit.

Why it matters

Potential benefit: If successful, this approach could better control disease during the pre‑CAR‑T period and increase the proportion of patients who go on to receive CAR‑T infusion.

How similar studies have performed: CD3×CD20 bispecific antibodies such as odronextamab have shown promising responses in relapsed/refractory B‑cell lymphomas, but their use specifically as pre‑CAR‑T bridging is relatively new and still being studied.

Eligibility criteria

Inclusion Criteria:

* 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
* Patients with bone marrow involvement or splenic sequestration: Platelet count ≥ 25 x 10\^9 /L
* Patients with bone marrow involvement or splenic sequestration: Hg ≥ 7.0 g/dL
* Patients with bone marrow involvement or splenic sequestration: ANC ≥ 0.5 x 10\^9 /L
* Negative serum pregnancy test within 2 days of initiating odronextamab for women of childbearing potential (WOCBP), defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
* Fertile male and WOCBP patients must be willing to use highly effective contraceptive methods from study recruitment to at least 6 months after the CAR T-cell infusion
* Patients must not provide egg or sperm donation until at least 6 months after the completion of the last dose of Odron

Exclusion Criteria:

* 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
* Evidence of significant concurrent disease or medical condition that could interfere with the conduct of the study, or put the patient at significant risk including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) and/or significant pulmonary disease (e.g., obstructive pulmonary disease and history of symptomatic bronchospasm)
* Ongoing systemic corticosteroid treatment, with the exception of corticosteroid use for other (non-tumor and non-immunosuppressive) indications up to a maximum of 10 mg/day of prednisone or equivalent. A short course of corticosteroid for lymphoma disease control during screening is allowed
* Infection with human immunodeficiency virus (unless viral load is undetectable and CD4 count ≥ 400) or chronic infection with hepatitis B virus or hepatitis C virus. Patients with hepatitis B (hepatitis B surface antigen positive \[HepBsAg+\]) with controlled infection were permitted upon consultation with the physician managing the infection
* Known hypersensitivity to both allopurinol and rasburicase
* Pregnant or breast-feeding women
* Administration of live vaccination within 28 days of first administration of study drug

Where this trial is running

Seattle, Washington

• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Mengyang Di, MD, PhD — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Mengyang Di, MD, PhD

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