Odronextamab + CAR-T Cell Therapy for Diffuse Large B-Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Davis

Must not be taking: Antiretrovirals, Corticosteroids

Disqualifiers: CNS lymphoma, Active infection, Recent surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 32

Duration: Up to 2 years

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug odronextamab can enhance the effectiveness of CAR-T cell therapy (a type of immunotherapy) for patients with diffuse large B-cell lymphoma (DLBCL) that has recurred or not responded to previous treatments. Odronextamab is designed to help the immune system identify and destroy cancer cells. Participants will receive odronextamab before and after the standard CAR-T cell therapy to determine if it improves treatment outcomes. This trial may suit individuals with DLBCL that hasn't improved with at least two prior treatments and who qualify for CAR-T cell therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like systemic corticosteroids above a specific dose and some experimental drugs are not allowed. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that odronextamab is generally well-tolerated in patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL). In studies, most side effects were manageable with supportive care. Only one patient experienced a severe immune reaction called cytokine release syndrome, which can cause fever and other symptoms.

Evidence indicates that CAR-T cell therapy effectively treats DLBCL, often resulting in strong and lasting improvements in patients who did not respond well to other treatments. The safety profile is considered manageable, with most patients experiencing mild to moderate side effects.

Both treatments have shown promise in previous studies, but potential participants should discuss all risks and benefits with their healthcare team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Odronextamab combined with CAR-T cell therapy for diffuse large B-cell lymphoma because it offers a novel approach by combining a bispecific antibody with cell therapy. Odronextamab is unique in that it targets both CD20 on B-cells and CD3 on T-cells, directing the immune system to attack the cancer cells more effectively. This dual-targeting could potentially enhance the body's ability to eliminate lymphoma cells compared to standard treatments like rituximab and traditional chemotherapy. Additionally, the integration with CAR-T cell therapy may provide a powerful one-two punch against the disease, potentially offering better outcomes for patients who don't respond to existing therapies.

What evidence suggests that odronextamab and CAR-T cell therapy could be effective for diffuse large B-cell lymphoma?

Research has shown that odronextamab, which participants in this trial may receive, may help treat patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In studies, about 31.7% of patients experienced a complete response (CR), meaning their cancer disappeared. The treatment was generally safe when combined with supportive care. CAR T-cell therapy, another treatment option in this trial, has also proven effective for DLBCL, offering long-term remissions with manageable side effects. Together, these treatments could be a strong option for those whose lymphoma hasn't responded to other treatments. ^{1 4 5 6 7}

Who Is on the Research Team?

Joseph M Tuscano

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for patients with a type of blood cancer called diffuse large B-cell lymphoma (DLBCL) that has either returned after treatment or hasn't responded to previous therapies. It's specifically for those who are candidates for CAR T-cell therapy, which is often used when other treatments don't work.

Inclusion Criteria

Life expectancy ≥ 3 months

Leukocytes ≥ 2,500/µL

Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

Exclusion Criteria

Pregnancy or lactation

Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she/they were to participate in the study or confounds the ability to interpret data from the study as determined by the study principal investigator (PI) or enrolling physician

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive odronextamab intravenously on specified days of each cycle, with cycles repeating every 21 days initially and then every 28 days for up to 2 years

Up to 2 years

Multiple visits per cycle (in-person)

CAR T-cell Therapy

Participants receive standard of care CAR T-cell therapy if disease assessment shows less than a complete response after cycle 4 or progressive disease after cycle 5

1 cycle

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

Follow-up at 30 days then every 4 months

What Are the Treatments Tested in This Trial?

Interventions

• Chimeric Antigen Receptor T-Cell Therapy
• Odronextamab

Trial Overview The study tests odronextamab, a dual-targeting antibody, given before and after standard CAR T-cell therapy in DLBCL patients. The goal is to see if this approach can boost the immune system's ability to fight cancer by helping T-cells identify and destroy B-cells involved in the disease.

How Is the Trial Designed?

Group I: Treatment (odronextamab, CAR T-cell therapy) Experimental Treatment 2 Interventions

Patients receive odronextamab IV over 1-4 hours on days 1, 2, 8, 9, 15, and 16 of cycle 1, on days 1, 8, and 15 of cycles 2-4 then on days 1 and 15 of subsequent cycles until achievement of durable CR. Cycles repeat every 21 days in the absence of durable CR, disease progression, or unacceptable toxicity. Patients with durable CR for ≥ 9 months may then receive odronextamab IV over 1-4 hours on day 1 of each subsequent cycle. These cycles repeat every 28 days for up to a total of 2 years in the absence of disease progression or unacceptable toxicity. Patients receive SOC CAR T-cell therapy if disease assessment shows less than a CR after cycle 4, or after cycle 5 if disease assessment shows PD any time after cycle 5.

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Joseph Tuscano

Lead Sponsor

Trials

8

Recruited

180+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

CAR T-cell therapy is an important treatment option for patients with refractory or relapsed diffuse large B-cell lymphoma, providing a targeted approach to combat this aggressive cancer.

The review discusses the criteria for selecting patients for CAR T-cell therapy and emphasizes the importance of bridging therapy and timing to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for the management of refractory/relapsed high-grade B-cell lymphoma: a practical overview. Mohty, M., Dulery, R., Gauthier, J., et al.[2023]

Odronextamab, a bispecific antibody targeting CD20 and CD3, has shown promising results in patients with relapsed/refractory B-cell non-Hodgkin lymphoma, achieving durable complete responses in two patients for over 2 years after treatment.

The treatment was well-tolerated, with no severe cytokine release syndrome or neurological adverse events reported, indicating a manageable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete responses to odronextamab in two patients with diffuse large B-cell lymphoma refractory to chimeric antigen receptor T-cell therapy. Weinstock, M., Elavalakanar, P., Bright, S., et al.[2023]

The novel CD19-PD-1/CD28 chimeric antigen receptor (CAR) T-cell therapy showed improved T-cell proliferation and effectiveness in killing PD-L1+ B-cell lymphoma cells, demonstrating enhanced efficacy compared to standard CD19 CAR T cells.

In a phase Ib study involving 17 adult patients with refractory or relapsed B-cell lymphoma, 58.8% of patients achieved an objective response, with 41.2% reaching complete remission, and the treatment was well-tolerated with no severe side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1-positive B-Cell Lymphoma. Liu, H., Lei, W., Zhang, C., et al.[2022]

In a study involving 9 patients with refractory/relapsed B cell lymphoma, a novel anti-CD19 CAR T cell therapy showed a high overall response rate of 77.8%, with 55.6% achieving complete remission.

The treatment demonstrated a favorable safety profile, with only 11.1% of patients experiencing severe cytokine release syndrome and neurotoxicity, while some patients maintained complete remission for over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Liu, X., Zhang, Y., Li, K., et al.[2021]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

Odronextamab, a bispecific antibody targeting CD20 and CD3, shows early promise in treating relapsed/refractory diffuse large B cell lymphoma (DLBCL), but many patients still do not achieve complete responses.

The addition of REGN5837, which engages CD28 on T cells, significantly enhances the antitumor activity of odronextamab in preclinical models, suggesting a potential chemotherapy-free treatment strategy for DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD22-targeted CD28 bispecific antibody enhances antitumor efficacy of odronextamab in refractory diffuse large B cell lymphoma models. Wei, J., Montalvo-Ortiz, W., Yu, L., et al.[2022]

Odronextamab, a bispecific antibody targeting CD20 and CD3, has shown adequate safety and tolerability in an ongoing first-in-human study for patients with relapsed/refractory B-cell non-Hodgkin lymphoma, indicating its potential as a therapeutic option.

Preclinical studies demonstrated that effective concentrations of odronextamab for inhibiting tumor growth in mouse models can inform dose escalation strategies for clinical trials, suggesting a translational approach to optimize dosing in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational findings for odronextamab: From preclinical research to a first-in-human study in patients with CD20+ B-cell malignancies. Zhu, M., Olson, K., Kirshner, JR., et al.[2022]

In a study involving 11 patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the combination of CD19 CAR-T cells and the anti-PD-1 antibody nivolumab was found to be safe, with no dose-limiting toxicities and manageable side effects like cytokine release syndrome in a minority of patients.

The treatment showed promising efficacy, achieving an objective response rate of 81.81% and a complete response rate of 45.45%, indicating strong anti-lymphoma activity that warrants further investigation in larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma. Cao, Y., Lu, W., Sun, R., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39822464/

Chimeric Antigen Receptor (CAR) T-cell Therapy in the ... CAR T-cell therapy has shown very promising results in the treatment of refractory or relapsed diffuse large B-cell lymphoma (DLBCL).

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19004

Long-term outcomes of CAR-T cell therapy in DLBCL. This systematic review underscore the significant long-term benefits and challenges of CD19 CAR-T cell therapy for diffuse large B-cell lymphoma (DLBCL).

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723016391

Real-World Outcomes with Chimeric Antigen Receptor T ... Our meta-analysis indicates that CAR-T therapies have manageable safety profiles and are effective in a wide range of patients with r/r LBCL.

4. nature.com nature.com/articles/s41571-023-00754-1

Long-term outcomes following CAR T cell therapy The data demonstrate that CD19-targeted CAR T cells can induce prolonged remissions in patients with B cell malignancies, often with minimal long-term ...

5. mdpi.com mdpi.com/2673-6357/6/1/3

Real-World Outcomes of Anti-CD19 Chimeric Antigen ... Landmark clinical trials have demonstrated the efficacy and safety of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for patients with R/R DLBCL, ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7028

Analysis of real-world (RW) AE reporting from the FDA ... Background: CAR T cell therapies have emerged as effective treatment options with deep and durable responses in patients (pt) with DLBCL.

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2840401

Access to CAR T Therapy in Patients With Diffuse Large B ... This case-control study evaluates the delay in treating relapsed or refractory diffuse large B-cell lymphoma due to distant access to ...