Epcoritamab for Diffuse Large B-Cell Lymphoma

Overseen By Julie E. Haydu, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: CD20/CD3 bispecifics, Anti-CD19 CAR T-cells

Disqualifiers: CNS involvement, Uncontrolled infection, 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: Unknown

Duration: Up to 24 months

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have used an investigational drug or approved systemic lymphoma therapy within 28 days before the first dose. Steroids for lymphoma control are allowed but must be stopped at least 7 days before starting the study drug.

What data supports the effectiveness of the drug Epcoritamab for treating Diffuse Large B-Cell Lymphoma?

Epcoritamab has shown strong anti-tumor activity in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL), with studies reporting overall response rates of 55.6% and complete response rates of 44.4%. It works by engaging T-cells to target and kill cancerous B-cells, and has been effective even in patients who did not respond to previous treatments. ^{1 2 3 4 5}

Is Epcoritamab safe for humans?

Epcoritamab has shown a manageable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma, with common side effects including cytokine release syndrome (a reaction from the immune system), injection-site reactions, infections, and low white blood cell counts. Most side effects were mild and resolved without stopping treatment. ^{1 2 3 4 5}

How is the drug Epcoritamab different from other treatments for diffuse large B-cell 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 less invasive than traditional intravenous methods. This drug is particularly novel for patients with relapsed or refractory diffuse large B-cell lymphoma who have already undergone multiple treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this study is to measure the efficacy of the study drug, epcoritamab, in participants with relapsed/refractory large B-cell lymphoma.

Research Team

Julie E. Haydu, MD, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for individuals with relapsed or refractory large B-cell lymphoma, a type of cancer. Participants should have experienced the condition returning after treatment or not responding to previous treatments.

Inclusion Criteria

My condition worsened or didn't respond after one treatment.

My organs and bone marrow are functioning well.

I can take care of myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

I have previously received a CD20/CD3 bispecific antibody treatment.

I have had a stem cell transplant before.

I have an autoimmune disease that is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive epcoritamab as a subcutaneous injection on cycle 1-3 days 1, 8, 15, and 22, cycle 4-9 days 1 and 15, and cycle 10 and onwards day 1. Dexamethasone is given during initial doses.

Up to 24 months

Frequent visits during initial cycles, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up for up to 24 months post-treatment or until disease progression or withdrawal.

24 months

Long-term follow-up

Participants may be followed annually for survival status after 24 months or at time of progression.

Annually

Treatment Details

Interventions

• Epcoritamab

Trial Overview The study is testing the effectiveness of epcoritamab, which is potentially a new option for treating this form of lymphoma. The focus is on how well it works in patients who have already tried other treatments without success.

Participant Groups

Group I: Epcoritamab Experimental Treatment 1 Intervention

Epcoritamab will be a subcutaneous injection on cycle 1-3 days 1, 8, 15, and 22, cycle 4-9 days 1 and 15, and cycle 10 and onwards day 1. Participants in a complete response will discontinue epcoritamab therapy after 12 cycles. Participants in a partial response or with stable disease at 1 year will continue epcoritamab and will discontinue at 18 or 24 months if in a complete response by those timepoints, otherwise they will continue until progression or intolerance. Dexamethasone (prophylactic corticosteroid) will be given during initial doses of study treatment. Dexamethasone will be taken either once daily or twice daily while receiving epcoritamab. A drug diary will be provided to participants to document information about dexamethasone being taken.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

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 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]

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

Epcoritamab: First Approval. [2023]

2. 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]

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. 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]

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

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