Epcoritamab for Follicular Lymphoma

Overseen By Gottfried von Keudell, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Beth Israel Deaconess Medical Center

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Cardiac conditions, Neurologic conditions, CNS involvement, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 12 months

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being done to see if epcoritamab is effective in treating follicular lymphoma as a second line of treatment. The name of the study drug in this research study is: -Epcoritamab (a type of antibody)

Do I need to stop my current medications to join the trial?

The trial requires that you stop any prior anti-lymphoma therapy at least 4 weeks before starting epcoritamab. If you are on immunosuppressive therapy for non-lymphoma-related reasons, you must stop it 28 days before starting the trial. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Epcoritamab for treating follicular lymphoma?

Research shows that Epcoritamab, a drug that helps the body's immune cells target and kill cancer cells, has shown strong anti-tumor activity in patients with follicular lymphoma, even if they have had previous treatments. In studies, it effectively killed cancer cells in a significant number of patients with this type of lymphoma. ^{1 2 3 4 5}

How is the drug Epcoritamab unique for treating follicular lymphoma?

Epcoritamab is unique because it is a bispecific antibody that engages T-cells to target and kill cancerous B-cells, and it is administered subcutaneously (under the skin), which is different from many other treatments that are given intravenously (through a vein). This drug has shown strong anti-tumor activity even in patients who have previously been treated with other CD20-targeted therapies. ^{1 2 3 5 6}

Research Team

Gottfried Von Keudell, MD, PhD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

This trial is for adults with follicular lymphoma who didn't fully respond to initial treatment. They should have a life expectancy over 2 years, good organ function, and no recent severe illnesses or drug abuse. Participants must not be pregnant, agree to use birth control, and have had only one prior therapy.

Inclusion Criteria

Agreement not to donate eggs (ova, oocytes) or sperm for assisted reproduction during and after the trial

My cancer has either shrunk or not grown after initial treatment.

Life expectancy of greater than 2 years

Exclusion Criteria

Current alcohol or drug abuse, psychiatric illness, or unstable social situation

I have not been hospitalized for an infection in the last 4 weeks.

History of allergic reactions to compounds similar to epcoritamab

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Epcoritamab for up to 12 cycles, with varying frequency of administration

12 months

Frequent visits during cycles 1-3, less frequent in later cycles

Follow-up

Participants are monitored for safety and effectiveness every 3 months for 2 years or until disease worsens

24 months

Every 3 months

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival up to 5 years

Up to 5 years

Treatment Details

Interventions

• Epcoritamab

Trial Overview The study tests Epcoritamab as a second-line treatment for follicular lymphoma. It's an antibody that targets the cancer cells. Patients will receive this medication to see if it can improve their condition after other treatments haven't led to complete remission.

Participant Groups

Group I: Epcoritamab Experimental Treatment 1 Intervention

35 participants will be enrolled and will complete study procedures as follows: * Baseline visit with imaging (CT, MRI or PET scan) and bone marrow biopsy. * Imaging after Cycles 3 and 6 only. * Cycles 1-3: --Days 1, 8, 15 and 22 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily * Cycles 4-9: --Days 1 and 15 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily * Cycles 10-12: --Day 1 of 28 day cycles: Predetermined dose of Epcoritamab 1x daily * End of Treatment visit with imaging and bone marrow biopsy. * Follow up: every 3 months for 2 years or until disease worsens. * Off study visit with imaging.

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?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

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

Findings from Research

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]

Epcoritamab, a bispecific antibody targeting CD3 and CD20, was found to be safe and well-tolerated in 73 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, with no dose-limiting toxic effects and a recommended phase 2 dose established at 48 mg.

The treatment showed promising efficacy, with an overall response rate of 68% in patients with diffuse large B-cell lymphoma and 90% in those with follicular lymphoma, indicating its potential as a viable therapy for these difficult-to-treat conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Hutchings, M., Mous, R., Clausen, MR., et al.[2021]

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]

Follicular lymphoma (FL) is a common B-cell cancer that is generally slow-growing but incurable, and optimal management strategies are still being developed to improve patient outcomes.

Current treatments, including anti-CD20 antibodies combined with chemotherapy, show similar overall survival rates, but ongoing research into new therapies, especially for patients with early relapses, may offer better options for managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel treatment approaches and future perspectives in follicular lymphoma. Sutamtewagul, G., Link, BK.[2020]

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, a bispecific antibody targeting CD3 and CD20, demonstrated a 55.6% overall response rate and a 44.4% complete response rate in 36 Japanese patients with relapsed or refractory CD20+ B-cell non-Hodgkin's lymphoma after a median follow-up of 8.4 months.

The treatment had a manageable safety profile, with cytokine release syndrome being the most common adverse event (83.3%), primarily low grade, and all cases resolved without leading to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma. Izutsu, K., Kumode, T., Yuda, J., et al.[2023]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. [2021]

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

Epcoritamab: First Approval. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Novel treatment approaches and future perspectives in follicular lymphoma. [2020]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma. [2023]