Odronextamab + Cemiplimab for Aggressive B-Cell Lymphoma

(CLIO-1 Trial)

Not currently recruiting at 53 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regeneron Pharmaceuticals

Must be taking: Anti-CD20 antibody

Must not be taking: Immunosuppressive treatments

Disqualifiers: CNS lymphoma, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two experimental drugs, odronextamab and cemiplimab, for treating aggressive B-cell lymphoma that has returned or resisted other treatments. The main goal is to assess the safety and tolerability of these drugs when used together and to determine the best dosage. Researchers aim to evaluate the drugs' effectiveness, potential side effects, and the body's reaction over time. Individuals with aggressive B-cell lymphoma who have tried at least two other treatments, including an anti-CD20 antibody, may qualify for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive these new drugs.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research is examining the safety and tolerability of combining two drugs, odronextamab and cemiplimab, for treating aggressive B-cell lymphoma. This is crucial for patients whose disease has returned or not responded to other treatments. Previous studies have assessed patient tolerance to these drugs. Results indicate that most people tolerate them well, though some side effects have been noted. Common side effects include fatigue, fever, and injection site reactions. More serious side effects can occur but are less common.

Odronextamab is an experimental drug that helps the immune system identify and attack cancer cells, while cemiplimab aims to strengthen the body's defense against cancer. The current research seeks to determine the right dosage and observe how the body reacts to these drugs.

As this is an early-stage study, the primary goal is to understand potential risks and side effects. This ensures the combination is safe for testing in more patients later on. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about odronextamab and cemiplimab for treating aggressive B-cell lymphoma because they offer a new approach compared to standard chemotherapy and targeted therapies like rituximab. Odronextamab is a bispecific antibody, meaning it can simultaneously bind to cancer cells and immune cells, potentially enhancing the body's ability to attack the cancer. Cemiplimab is a checkpoint inhibitor that helps the immune system recognize and fight cancer cells more effectively. Together, these drugs could provide a more targeted and immune-based strategy, possibly leading to better outcomes for patients with fewer side effects than traditional treatments.

What evidence suggests that this trial's treatments could be effective for aggressive B-cell lymphoma?

This trial will evaluate the combination of two drugs, odronextamab and cemiplimab, for treating aggressive B-cell lymphoma. Research has shown that this combination might help treat the disease. Early results indicate that patients with hard-to-treat diffuse large B-cell lymphoma have experienced promising outcomes, with some showing no detectable cancer after treatment. This drug combination boosts the body's immune response against cancer and prevents T-cells, vital for fighting the disease, from becoming worn out. However, further studies are needed to confirm the overall effectiveness and safety of this combination. ^{1 2 3 4 6}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with aggressive B-cell lymphoma that's come back or hasn't responded to treatment, and no standard care options are left. They must have a life expectancy over 6 months, good organ function, measurable disease by imaging, and be able to follow the study plan. Excluded are those with certain infections (HIV/hepatitis), CNS lymphoma involvement, allergy to tetracycline antibiotics, unwillingness to use contraception, recent significant autoimmune disease needing immunosuppressants, prior specific cancer treatments including stem cell transplant or PD-1/PD-L1 inhibitors (unless beneficial), known allergies relevant here.

Inclusion Criteria

My organs are working well.

My bone marrow is working well.

I am fully active or can carry out light work.

Exclusion Criteria

I do not have an uncontrolled infection like HIV or hepatitis.

History of hypersensitivity to any compound in the tetracycline antibiotics group

You are pregnant or currently breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Safety assessment of odronextamab in combination with cemiplimab and selection of recommended phase 2 dose regimen(s)

8-12 weeks

Dose Expansion

Administration of the recommended phase 2 dose (RP2D) regimen of the combination treatment

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• REGN1979

Trial Overview The trial is testing how safe and tolerable two experimental drugs—odronextamab (REGN1979) and cemiplimab (REGN2810)—are when combined in adults with relapsed/refractory aggressive B-cell lymphoma. It aims to find the best dose regimen for this combination therapy while also examining side effects effectiveness against the disease levels of drug in blood over time potential development of antibodies against these drugs.

How Is the Trial Designed?

Group I: Dose expansion phase Experimental Treatment 2 Interventions

RP2D administration of the combination treatment.

Group II: Dose escalation phase Experimental Treatment 2 Interventions

Safety assessment of odronextamab in combination with cemiplimab and selection of recommended phase 2 dose (RP2D) regimen(s) for the combination of odronextamab and cemiplimab.

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

In a study of 24 patients with relapsed or refractory follicular or mantle cell lymphoma, 131 I-rituximab demonstrated significant efficacy, with 9 patients achieving complete response and 8 achieving partial response after treatment.

The treatment showed a median progression-free survival of 5.9 months and overall survival of 37.9 months, although it was associated with common hematologic toxicities, including severe thrombocytopenia and neutropenia in two-thirds of the cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma. Jang, YJ., Lim, SM., Lee, I., et al.[2023]

In a phase III trial involving 36 Japanese patients with relapsed indolent non-Hodgkin lymphoma, the combination of lenalidomide and rituximab (R2) significantly improved progression-free survival (PFS) compared to rituximab plus placebo, with a hazard ratio of 0.32.

While R2 showed superior efficacy with a median PFS not reached versus 16.5 months for the placebo group, it also had a higher incidence of grade 3/4 adverse events (67% vs. 22%), mainly due to increased neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Japanese patients from the AUGMENT phase III study of lenalidomide + rituximab (R2) vs. rituximab + placebo in relapsed/refractory indolent non-Hodgkin lymphoma. Izutsu, K., Minami, Y., Fukuhara, N., et al.[2020]

The combination of rituximab and lenalidomide (R2) significantly improves treatment efficacy for recurrent non-Hodgkin lymphoma compared to rituximab alone, leading to its approval for use in previously treated patients with follicular and marginal zone lymphoma.

R2 has a manageable safety profile, with common adverse events including grade 3/4 neutropenia, skin rashes, and gastrointestinal issues, indicating that while it is effective, careful monitoring and management of side effects are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Adverse Events From the Combination of Rituximab and Lenalidomide in the Treatment of Patients With Follicular and Low-Grade Non-Hodgkin Lymphoma. Cheson, BD., Morschhauser, F., Martin, P.[2021]

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]

Rituximab (RTX) is a widely used monoclonal antibody for treating diffuse large B-cell lymphoma, often combined with other drugs in the R-CHOP regimen, but some patients experience suboptimal responses or resistance.

New developments in CD20-targeting monoclonal antibodies, including second- and third-generation agents like ofatumumab and obinutumumab, are being actively researched to improve treatment outcomes for B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. Cang, S., Mukhi, N., Wang, K., 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]

Lenalidomide, especially when combined with rituximab (the 'R(2)' regimen), shows enhanced efficacy in treating indolent B-cell and mantle cell lymphomas, even in patients resistant to rituximab, while maintaining a manageable safety profile.

The most common serious side effect is asymptomatic neutropenia, which can be managed through dose adjustments, and while immune-related symptoms like rash are more frequent with the R(2) regimen, they are generally low-grade and manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. Ruan, J., Shah, B., Martin, P., et al.[2020]

In a phase 1b trial involving 36 patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the combination of obinutuzumab, atezolizumab, and polatuzumab vedotin (G-atezo-pola) showed limited efficacy, with complete response rates of 33% and 14% for follicular lymphoma patients at different doses, and only 13% for diffuse large B-cell lymphoma patients receiving rituximab-atezo-pola.

Safety concerns were significant, particularly with G-atezo-pola, where 62% of follicular lymphoma patients experienced severe adverse events, including two deaths, leading to the decision not to pursue further development of either combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD20-atezolizumab-polatuzumab vedotin in relapsed/refractory follicular and diffuse large B-cell lymphoma. Topp, MS., Eradat, H., Florschütz, A., et al.[2023]

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]

In a study of 379 patients with diffuse large B-cell lymphoma (DLBCL), the treatment regimen R-ACVBP showed a significant survival advantage over R-CHOP, particularly for patients with non-germinal center B-cell-like (non-GCB) tumors, indicating that tumor classification can influence treatment outcomes.

The Hans algorithm for subclassifying tumors was found to be a significant predictor of progression-free survival and overall survival, suggesting it could be used as a biomarker to identify patients who would benefit from the more intensive R-ACVBP treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. Molina, TJ., Canioni, D., Copie-Bergman, C., et al.[2019]

Odronextamab, a bispecific antibody targeting CD20 and CD3, demonstrated a manageable safety profile with no dose-limiting toxicities observed during a phase 1 trial involving 145 heavily pretreated patients with B-cell non-Hodgkin lymphoma.

The treatment showed promising efficacy, with an overall objective response rate of 51%, and particularly high response rates in patients with follicular lymphoma (91%) and in those with diffuse large B-cell lymphoma who had not received prior CAR T therapy (53%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odronextamab, a human CD20×CD3 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. Bannerji, R., Arnason, JE., Advani, RH., et al.[2023]

A comprehensive analysis of 63 treatment regimens for relapsed/refractory diffuse large B-cell lymphoma (r/rDLBCL) showed that combination therapies significantly improve overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared to monotherapy.

Specific regimens, such as rituximab combined with inotuzumab ozogamicin and R-BEAM+ASCT, demonstrated particularly high efficacy, with median overall survival times ranging from 25 to 48.2 months, highlighting the potential of these combinations in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative evaluation of therapy options for relapsed/refractory diffuse large B-cell lymphoma: A model-based meta-analysis. Li, T., Yu, J., Hou, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02651662

NCT02651662 | A Study to Learn How Safe and Tolerable ... The aim of the study is to see how safe and tolerable the study drugs are, and to define the recommended dose regimen for the combination with odronextamab.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428946/

PB2366: TRIAL IN PROGRESS: PHASE 1 ... This Ph 1 trial is determining the tolerability and preliminary clinical efficacy of odronextamab plus cemiplimab to treat pts with R/R aggressive B-NHL.

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3100/503773/Trial-in-Progress-Phase-1-Trial-Evaluating-the

Trial in Progress: Phase 1 Trial Evaluating the Safety and ... Combining odronextamab and cemiplimab provides an attractive therapeutic opportunity to improve anti-tumor efficacy while restricting T-cell exhaustion.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123097021

Phase 1 Trial Evaluating the Safety and Tolerability of ... Here, we investigate whether the addition of cemiplimab to odronextamab can improve the depth and durability of response in patients with previously treated ...

5. withpower.com withpower.com/trial/phase-1-lymphoma-2016-d06fd

Odronextamab + Cemiplimab for Aggressive B-Cell ... Odronextamab has shown promising results in patients with difficult-to-treat diffuse large B-cell lymphoma, with some achieving complete responses lasting over ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2016-01243

A Study to Learn How Safe and Tolerable Odronextamab ... A Study to Learn How Safe and Tolerable Odronextamab and Cemiplimab Are in Adult Patients With B-cell Malignancies. Trial Status: closed to accrual. Open all ...