Epcoritamab for Diffuse Large B-Cell Lymphoma

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called epcoritamab to evaluate its effectiveness for individuals with large B-cell lymphoma that has returned or is unresponsive to previous treatments. Epcoritamab is administered through injections, and the trial aims to assess its effectiveness and safety. Individuals with this specific type of lymphoma who have previously tried one treatment involving certain drugs may be suitable for the study. Participants should have measurable disease and not qualify for more aggressive treatments like high-dose chemotherapy and stem cell transplants. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that epcoritamab is likely to be safe for humans?

Research has shown that the safety of epcoritamab for treating diffuse large B-cell lymphoma is manageable. In one study with over two years of follow-up, patients tolerated the treatment well.

Another study suggested that epcoritamab can be safely administered outside of a hospital, potentially eliminating the need for overnight stays. This indicates it is generally well-tolerated.

Epcoritamab is also approved in the United States for patients whose diffuse large B-cell lymphoma has returned or not responded to other treatments. This approval reflects confidence in its safety for this condition.

Overall, evidence supports that epcoritamab is relatively safe for patients, with manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for diffuse large B-cell lymphoma, like chemotherapy and targeted therapies such as rituximab, aim to attack cancer cells in general. However, epcoritamab works differently by specifically targeting and engaging the body's immune system to attack these lymphoma cells. Epcoritamab is administered as a subcutaneous injection, which can be more convenient than intravenous treatments, allowing for potentially easier integration into patients' lives. Researchers are excited about epcoritamab because its innovative mechanism may offer new hope for patients who haven't responded well to existing therapies.

What evidence suggests that epcoritamab might be an effective treatment for large B-cell lymphoma?

Research has shown that epcoritamab, the treatment under study in this trial, may effectively treat diffuse large B-cell lymphoma, particularly in patients unresponsive to other treatments. In one study, 64.3% of patients improved, with 47.6% achieving a complete response, meaning their cancer was no longer detectable. Another study reported similar results, with a complete response rate of 47%. Epcoritamab targets specific proteins on cancer cells, aiding the immune system in identifying and destroying them. These findings suggest that epcoritamab could be a promising option for those with relapsed or hard-to-treat large B-cell lymphoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Julie E. Haydu, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/146/18/2177/546196/Real-world-outcomes-of-patients-with-aggressive-B

Real-world outcomes of patients with aggressive B-cell ... A total of 201 of 245 patients (82.0%) were efficacy-evaluable (124 treated with epcoritamab [80%], and 77 treated with glofitamab [87%]).

2. ir.genmab.com ir.genmab.com/news-releases/news-release-details/genmab-announces-updated-results-phase-2-epcorer-nhl-6-study

Genmab Announces Updated Results from Phase 2 ... ... diffuse large B-cell lymphoma (DLBCL) in an outpatient setting; Results showed that 92% of patients with R/R DLBCL received the first full ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40434509/

Efficacy and safety of epcoritamab in Japanese patients ... Results: As of July 12, 2024, 36 patients received epcoritamab (median follow-up, 36.7 months). Overall/complete response rates were 56%/47%.

4. news.abbvie.com news.abbvie.com/2025-09-03-AbbVie-Announces-Updated-Results-From-Phase-2-EPCORE-R-NHL-6-Study-Evaluating-the-Potential-for-Outpatient-Monitoring-of-Epcoritamab-in-Patients-With-Relapsed-Refractory-R-R-Diffuse-Large-B-Cell-Lymphoma-DLBCL

AbbVie Announces Updated Results From Phase 2 ... The study also showed an overall response rate (ORR) of 64.3% and a complete response (CR) rate of 47.6%, at a median follow-up of 5.8 months, ...

5. nature.com nature.com/articles/s41375-024-02410-8

Epcoritamab in relapsed/refractory large B-cell lymphoma At data cutoff, 27 patients (17.2%) continued receiving study treatment and 21 (13.4%) patients had received epcoritamab for at least 24 months.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01725

Dose Expansion in a Phase I/II Trial - ASCO Publications Outcomes are poor for patients with relapsed or refractory large B-cell lymphoma (LBCL). This study evaluated the efficacy and safety of ...