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

Trial Summary

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.

What data supports the effectiveness of the drug Epcoritamab for treating Non-Hodgkin's Lymphoma?

Epcoritamab has shown strong anti-tumor activity in patients with different types of B-cell non-Hodgkin lymphoma, including those who did not respond to previous treatments. It has been conditionally approved in the USA for treating certain types of relapsed or hard-to-treat large B-cell lymphoma, demonstrating its potential effectiveness. ^{1 2 3 4 5}

What safety data exists for Siltuximab and Epcoritamab in humans?

Siltuximab has been studied for safety in patients with multicentric Castleman disease, showing common side effects like itching, weight gain, rash, high uric acid levels, and upper respiratory infections. There is no specific safety data available for Epcoritamab in the provided research. ^{6 7 8 9 10}

How is the drug Siltuximab + Epcoritamab unique for treating Non-Hodgkin's Lymphoma?

This drug combination is unique because it includes Siltuximab, which targets interleukin-6 (IL-6) to reduce inflammation, and Epcoritamab, which is a bispecific antibody that helps the immune system attack cancer cells. This dual approach may offer a novel way to treat Non-Hodgkin's Lymphoma by combining immune system activation with inflammation reduction. ^{7 11 12 13 14}

What is the purpose of this trial?

The goal of this clinical trial is to is to determine the safety, feasibility and efficacy of siltuximab prophylaxis of cytokine release syndrome and neurotoxicity occurring after epcoritamab subcutaneous administration for participants with large b-cell lymphoma (DLBCL) or follicular lymphoma (FL). Participants will receive siltuximab, prior to the injection of epcoritamab. Epcoritamab is administered in 28 day cycles for one year. After this injection, the physician will continue to watch participants for side effects and follow the condition for a minimum of 60 days.

Research Team

Taylor Brooks, MD

Principal Investigator

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Epcoritamab: First Approval. [2023]

3. United States 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Epratuzumab: targeting B-cell malignancies through CD22. [2017]

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. [2017]

8. United States 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Phase I/II trial of epratuzumab (humanized anti-CD22 antibody) in indolent non-Hodgkin's lymphoma. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin's lymphoma: phase I/II results. [2021]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Siltuximab: first global approval. [2021]

12. United States 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. [2017]

13. England pubmed.ncbi.nlm.nih.gov

Siltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma. [2017]

14. New Zealand pubmed.ncbi.nlm.nih.gov

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