Epcoritamab for Diffuse Large B-Cell Lymphoma

(EPCORE DLBCL-1 Trial)

Not currently recruiting at 313 trial locations

Overseen By Genmab A/S Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Genmab

Must not be taking: Bispecific antibodies, Investigational drugs

Disqualifiers: CNS tumor, Seizure disorder, Cardiac disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called epcoritamab to determine its safety and effectiveness for people with diffuse large B-cell lymphoma (DLBCL) that hasn't responded to past treatments, has grown, or has returned after treatment. Participants will receive either epcoritamab, injected under the skin, or standard chemotherapy, administered through an IV. This trial suits those who have tried at least one cancer therapy, cannot undergo a stem cell transplant, and have a specific type of DLBCL. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot have had chemotherapy or other cancer treatments (except certain antibodies) within 4 weeks before starting the trial. It's best to discuss your current medications with the trial team.

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

Research has shown that epcoritamab has been promising in earlier studies. In one study, 61% of patients experienced either a reduction or disappearance of their cancer. Another study involving Japanese patients reported similar results, with 56% responding to the treatment and 47% achieving complete remission.

Regarding safety, epcoritamab is generally well-tolerated. However, like any treatment, it can have side effects. Various studies have reported some patients experiencing side effects, but these are usually manageable. The fact that epcoritamab is in advanced clinical trials indicates it has already undergone significant safety testing, providing some reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for DLBCL?

Epcoritamab is unique because it targets CD3 and CD20 proteins on cells, which is different from traditional chemotherapy approaches that typically don't focus on specific proteins. This bispecific antibody brings T-cells directly to cancer cells, potentially offering a more precise attack against the diffuse large B-cell lymphoma. Researchers are excited about its potential to enhance the immune system's ability to fight cancer more effectively, potentially leading to fewer side effects compared to standard chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for DLBCL?

Research has shown that epcoritamab, one of the treatments studied in this trial, may help treat Diffuse Large B-Cell Lymphoma (DLBCL) that has returned or not responded to other treatments. In one study, 64.3% of patients experienced tumor reduction, and 47.6% saw their cancer disappear completely. Epcoritamab aids the immune system in attacking cancer cells. These findings suggest that epcoritamab could be a viable option for those who haven't succeeded with other treatments. Participants in this trial may receive either epcoritamab or the investigator's choice of chemotherapy. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with certain types of B-cell lymphoma, including Diffuse Large B-Cell Lymphoma (DLBCL), who have not responded to or are ineligible for a stem cell transplant. Participants must be in relatively stable health and have measurable disease by scans. They cannot join if they've had recent major surgery, CAR-T therapy, seizures requiring medication, heart issues, CNS tumors or involvement, prior CD3/CD20 bispecific antibody treatment.

Inclusion Criteria

My lymphoma has returned or didn't respond to treatment, and I've had at least one treatment that included anti-CD20.

My doctor expects me to live more than 2 months with standard treatment.

My lymphoma is CD20-positive and matches one of the specified types.

Exclusion Criteria

I have a serious heart condition.

My cancer affects my brain or spinal cord.

I have been treated with a specific antibody for CD3 and CD20.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Treatment

Participants receive either epcoritamab or investigator's choice chemotherapy. Epcoritamab is administered weekly for the first 3 months, then bi-weekly for 6 months, and then every 28 days. Chemotherapy options include R-GemOx or BR with specific schedules.

4-6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment until death.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Investigator's Choice Chemotherapy

Trial Overview The study compares the effectiveness of Epcoritamab—an antibody drug—against standard chemotherapy chosen by the investigator. Patients will be randomly assigned to receive either Epcoritamab or chemotherapy to see which works better for relapsed/refractory DLBCL after previous treatments failed.

How Is the Trial Designed?

Group I: Epcoritamab (GEN3013; DuoBody®CD3xCD20) Experimental Treatment 1 Intervention

Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met

Group II: Investigator's choice of chemotherapy Active Control 1 Intervention

R-GemOx will be administrated in Cycles of 28 days until maximum cycles completion or any of the discontinuation criteria is met BR will be administrated in Cycles of 21 days until maximum cycles completion or any of the discontinuation criteria is met

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?

Genmab

Lead 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

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

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 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, 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]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody-drug conjugate, has shown a 48.6% overall response rate in patients with relapsed, refractory diffuse large B-cell lymphoma, indicating its efficacy as a treatment option.

The drug has a tolerable safety profile, with common side effects including neutropenia and thrombocytopenia, leading to its recent FDA approval for treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. Furqan, F., Hamadani, M.[2022]

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. 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 ... In patients treated with epcoritamab following two or more lines of systemic therapy (n=50), with a median follow-up of 10.8 months, the study ...

3. epkinly.com epkinly.com/dlbcl/clinical-trial-results

DLBCL Clinical Trial Results Remission is possible. EPKINLY delivers powerful efficacy that can transform uncertainty into hope. The goal of EPKINLY is to help you achieve remission.

4. 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 ... The study also demonstrated 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 ...

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

Epcoritamab-bysp (Epkinly) – A phenomenal breakthrough ... In conclusion, Epcoritamab-bysp represents a significant breakthrough in the treatment of relapsed or refractory Diffuse Large B-cell Lymphoma ( ...

6. 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%.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025023766

Safety and Efficacy of Epcoritamab in Relapsed, Refractory ... Our study demonstrated pooled ORR of 73% in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, 71.7% for DLBCL and 82.5% for FL. However, ...

8. 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, ...