Siltuximab + Epcoritamab for Non-Hodgkin's Lymphoma

Overseen By Taylor Brooks, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Anti-infectives

Disqualifiers: Active CNS involvement, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, siltuximab and epcoritamab, for individuals with certain types of non-Hodgkin's lymphoma, specifically large B-cell lymphoma or follicular lymphoma. The main goal is to determine if siltuximab can prevent side effects like cytokine release syndrome (a severe immune reaction) when administered before epcoritamab. This trial is open to those who have tried at least two other treatments for their lymphoma but still experience issues. It may suit individuals dealing with frequent or worsening symptoms despite prior treatments. Participants will receive these treatments over a year and be monitored for any side effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

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

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

Research has shown that epcoritamab, a key component of the treatment, has been tested in patients with certain types of lymphoma. In studies, 63.1% of patients with large B-cell lymphoma responded well to epcoritamab, indicating its promising effectiveness.

Regarding safety, research has examined how well patients tolerate epcoritamab. As a bispecific antibody, it targets specific cells in the body. While it can cause side effects, these are closely monitored in clinical settings.

Siltuximab is used to manage a potential side effect called cytokine release syndrome, where the body reacts strongly to the treatment. This combination aims to reduce such reactions and enhance patient safety.

This trial is in the early stages, so the treatment's safety is still under close study. However, using siltuximab to prevent side effects demonstrates a focus on improving safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining siltuximab and epcoritamab for treating Non-Hodgkin's Lymphoma because this approach offers a fresh angle compared to standard treatments like chemotherapy and targeted therapies such as rituximab. Epcoritamab is a bispecific antibody that targets CD3 and CD20, engaging T-cells to attack cancer cells, which is a novel mechanism compared to traditional options. Meanwhile, siltuximab is an anti-IL-6 monoclonal antibody, potentially reducing inflammation and cytokine release syndrome, a common side effect of immune therapies. Together, these treatments could enhance the immune response against lymphoma while managing side effects, offering a promising new option for patients.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

Research shows that epcoritamab, a protein targeting two parts of cancer cells, has promising results in treating certain types of Non-Hodgkin's Lymphoma. In a study with patients whose large B-cell lymphoma returned or didn't respond to treatment, epcoritamab significantly reduced cancer in 63.1% of them. Additionally, 38% of these patients had no detectable cancer after treatment. In this trial, participants will receive a combination of siltuximab and epcoritamab. Although still being tested in this context, siltuximab might help lessen side effects of epcoritamab, such as cytokine release syndrome, a potentially dangerous immune reaction. Together, these treatments aim to improve outcomes for people with hard-to-treat lymphomas. ^{1 2 3 6 7}

Who Is on the Research Team?

Taylor Brooks, MD

Principal Investigator

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with large B-cell lymphoma or follicular lymphoma. Participants must be eligible to receive epcoritamab and are willing to be monitored for at least 60 days after treatment. Specific inclusion and exclusion criteria details were not provided.

Inclusion Criteria

I agree to not have unprotected sex or donate sperm.

I have been diagnosed with non-Hodgkin lymphoma.

I have DLBCL and have been treated with a therapy that includes an anti-CD20 drug.

Exclusion Criteria

I have cancer other than non-melanoma skin cancer or carcinoma in situ.

My condition is primary mediastinal B cell lymphoma.

I do not have any uncontrolled illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive prophylactic siltuximab followed by epcoritamab in 28-day cycles for up to 24 cycles

12-24 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 months

Long-term follow-up

Participants are monitored for long-term outcomes and adverse events

15 months

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Siltuximab

Trial Overview The study tests if siltuximab can prevent or treat cytokine release syndrome and neurotoxicity in patients receiving epcoritamab injections, over cycles of 28 days for one year.

How Is the Trial Designed?

Group I: Prophylactic siltuximab + epcoritamab Experimental Treatment 2 Interventions

Siltuximab Administration: • Participants will receive a single dose of prophylactic siltuximab, 11mg/kg, started 1 hour prior (+/- 60 minutes) to the infusion of epcoritamab. There is no planned dose escalation of siltuximab and epcoritamab dosing will be done following the standard planned ramp-up over the course of the first 3 weeks Epcoritamab Infusion: • The treatment regimen of epcoritamab is done in 28-day cycles. Epcoritamab is to be administered by subcutaneous injection. Participants can be treated for up to 24 cycles. Participants who achieve complete remission at the time of their disease response assessment after 12 cycles may be considered for early discontinuation of treatment.

Epcoritamab is already approved in United States, European Union for the following indications:

Approved in United States as Epkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Diffuse large B-cell lymphoma after two or more lines of systemic therapy

Approved in European Union as Tepkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Paolo Caimi, MD

Lead Sponsor

Trials

5

Recruited

170+

Taylor Brooks

Lead Sponsor

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Genmab

Industry Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

Recordati Rare Diseases

Industry Sponsor

Trials

14

Recruited

540+

RECORDATI GROUP

Industry Sponsor

Trials

13

Recruited

4,500+

Published Research Related to This Trial

Siltuximab was approved by the FDA for treating multicentric Castleman disease (MCD) in HIV-negative and HHV-8-negative patients, based on a randomized trial with 79 patients showing a significant response rate; 34% of those treated with siltuximab achieved a durable tumor and symptomatic response compared to none in the placebo group.

The treatment was generally well-tolerated, with common side effects including pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infections occurring in more than 10% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. Deisseroth, A., Ko, CW., Nie, L., et al.[2017]

Siltuximab is the first approved treatment for multicentric Castleman's disease (MCD) in both the US and EU, highlighting its significance in addressing this rare condition.

The drug was approved through expedited processes, including the FDA's priority review and the EU's accelerated assessment, indicating its potential effectiveness and the urgent need for treatment options in MCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Siltuximab: first global approval. Markham, A., Patel, T.[2021]

In a study of 79 patients with multicentric Castleman disease, treatment with siltuximab led to a significant 92% reduction in C-reactive protein (CRP) levels, indicating effective suppression of inflammation associated with the disease.

Siltuximab also improved anemia in patients, with 61% showing a hemoglobin response, and this effect was linked to a 47% decrease in hepcidin levels, suggesting that IL6 inhibition positively influences iron metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Inflammatory and Anemia-Related Biomarkers in a Randomized, Double-Blind, Placebo-Controlled Study of Siltuximab (Anti-IL6 Monoclonal Antibody) in Patients With Multicentric Castleman Disease. Casper, C., Chaturvedi, S., Munshi, N., et al.[2017]

Siltuximab, an antibody targeting interleukin-6 (IL-6), has shown promising results in treating multicentric Castleman disease but has been less effective in hematological malignancies like non-Hodgkin lymphoma and multiple myeloma, indicating a complex interaction between cancer cells and the immune response.

The review highlights potential future research directions for Siltuximab, particularly its use in early-stage multiple myeloma and possibly in treating Waldenström macroglobulinemia, suggesting that its therapeutic applications may expand beyond current uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Siltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma. Ferrario, A., Merli, M., Basilico, C., et al.[2017]

Epcoritamab is a bispecific antibody that targets CD3 and CD20, designed for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), and received conditional approval in the USA on May 19, 2023, for adult patients after at least two prior therapies.

The drug has also received a positive opinion in the EU and is under review in Japan, indicating its potential as a significant treatment option for patients with difficult-to-treat B-cell non-Hodgkin lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epcoritamab: First Approval. Frampton, JE.[2023]

Epcoritamab, a bispecific antibody targeting CD3 and CD20, showed a 63.1% overall response rate in 157 patients with relapsed or refractory large B-cell lymphoma, indicating its efficacy in this challenging patient population.

The treatment was generally well-tolerated, with manageable side effects; however, cytokine release syndrome was common (49.7%), and there was one reported fatality due to immune effector cell-associated neurotoxicity syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. Thieblemont, C., Phillips, T., Ghesquieres, H., et al.[2023]

Epratuzumab, a humanized anti-CD22 monoclonal antibody, has shown promise in treating both indolent and aggressive lymphomas, demonstrating good tolerance and the ability to induce tumor regressions in early clinical trials.

Current trials are exploring the safety and effectiveness of epratuzumab in combination with rituximab and standard chemotherapy, with initial results indicating acceptable toxicity and potential as an adjunct therapy for lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell malignancies. Leonard, JP., Goldenberg, DM.[2017]

In a study of 65 patients with recurrent or refractory non-Hodgkin's lymphoma, the combination of epratuzumab and rituximab was well tolerated and showed an objective response rate of 47%, with the highest response in follicular lymphoma (64%).

The treatment demonstrated promising efficacy, particularly in patients with lower prognostic index scores, and the median duration of response was 16 months for follicular lymphoma, indicating potential long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. Strauss, SJ., Morschhauser, F., Rech, J., et al.[2017]

In a phase I study involving 67 patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease, siltuximab was found to be safe with no dose-limiting toxicities, and the most common side effects were manageable blood-related issues like thrombocytopenia and neutropenia.

Siltuximab showed promising efficacy, particularly in Castleman disease, where 86% of patients experienced improvement in clinical benefit response, and a recommended dose of 12 mg/kg every 3 weeks was established based on high response rates and effective C-reactive protein suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Kurzrock, R., Voorhees, PM., Casper, C., et al.[2022]

Epratuzumab, an anti-CD22 monoclonal antibody, was well tolerated in 55 patients with recurrent indolent non-Hodgkin's lymphoma, showing no dose-limiting toxicity and a mean serum half-life of 23 days.

The treatment demonstrated clinical activity, particularly in patients with follicular NHL, achieving an 18% overall objective response rate, with a notable 43% response rate at the 360 mg/m2 dose, suggesting this dosage warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of epratuzumab (humanized anti-CD22 antibody) in indolent non-Hodgkin's lymphoma. Leonard, JP., Coleman, M., Ketas, JC., et al.[2017]

In a study involving 82 patients with relapsed/refractory B-cell non-Hodgkin's lymphoma, veltuzumab was well tolerated with no severe drug-related side effects, demonstrating a favorable safety profile.

The treatment showed significant efficacy, particularly in follicular lymphoma, with 44% of patients achieving objective responses and a median duration of complete responses lasting 19.7 months, indicating its potential as a viable alternative to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin's lymphoma: phase I/II results. Morschhauser, F., Leonard, JP., Fayad, L., et al.[2021]

Epcoritamab, a bispecific antibody, showed strong efficacy in killing primary tumor cells from patients with newly diagnosed and relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), achieving median lysis rates of 65% to 84% across different lymphoma types.

The effectiveness of epcoritamab was consistent regardless of prior treatments, including CD20 monoclonal antibodies, indicating its potential as a treatment option for patients who have become resistant to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. van der Horst, HJ., de Jonge, AV., Hiemstra, IH., et al.[2021]

Siltuximab is the only approved treatment for idiopathic multicentric Castleman disease (iMCD), effectively reducing IL-6 levels and improving symptoms and overall well-being in patients.

In clinical trials, siltuximab demonstrated a good safety profile, with most side effects being mild and manageable, making it a significant advancement in treating this rare and serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Siltuximab: A Review in Idiopathic (Human Herpesvirus-8-Negative) Multicentric Castleman Disease. Lyseng-Williamson, KA.[2017]

Monoclonal antibody therapies targeting B cells, like anti-CD20 antibodies, have significantly improved treatment for B-cell non-Hodgkin's lymphoma, showing manageable side effects and distinct mechanisms of action compared to traditional chemotherapy.

Epratuzumab, a humanized anti-CD22 monoclonal antibody, shows promise in treating B-cell malignancies, with ongoing studies to determine its effectiveness both alone and in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epratuzumab: targeting B-cell malignancies through CD22. Coleman, M., Goldenberg, DM., Siegel, AB., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06447376

NCT06447376 | Study of Cytokine Release Syndrome ... Addition of siltuximab to the medications given before epcoritamab, may prevent, or reduce the severity, of CRS. Siltuximab is experimental because it is not ...

2. withpower.com withpower.com/trial/phase-1-syndrome-7-2024-1ae72

Siltuximab + Epcoritamab for Non-Hodgkin's Lymphoma Epcoritamab, a bispecific antibody targeting CD3 and CD20, showed a 63.1% overall response rate in 157 patients with relapsed or refractory large B-cell ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/epcoritamab?pn=1

Clinical Trials Using Epcoritamab - NCI Clinical Trials Using Epcoritamab. Review the clinical trials studying epcoritamab on this list and use the filters to refine the results by age and location.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10392166/

Epcoritamab-bysp (Epkinly) – A phenomenal breakthrough ... With 38% of patients receiving complete responses, the ORR was 61% (95% CI: 53, 69). The estimated median duration of response (DOR) was 15.6 ...

5. canjhealthtechnol.ca canjhealthtechnol.ca/index.php/cjht/article/view/PC0334r/2215

View of Epcoritamab (Epkinly) Additionally, with a current median overall survival (OS) of 6 months in this population, the experts considered a benefit of at least 6 months and 3 months ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04663347

NCT04663347 | Safety and Efficacy Trial of Epcoritamab ... The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1521692625000039

Bispecific antibody therapy for lymphoma OS for complete responders was 54 % at 24 months and 32 % at 36 months [40], demonstrating potential inferiority to Epcoritamab and Glofitamab within ...