Epcoritamab for Large B-Cell Lymphoma

Overseen By Kaitlin Kennard

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Abramson Cancer Center at Penn Medicine

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Organ transplant, CNS lymphoma, Autoimmune disease, Cardiovascular disease, 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: 6

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of the drug epcoritamab (also known as Epkinly or Tepkinly) for individuals with large B-cell lymphoma, particularly before and after CAR T cell therapy. Researchers aim to determine if epcoritamab can treat residual lymphoma remaining after CAR T cell treatment. It suits those who have not responded to standard therapies and have a confirmed diagnosis of large B-cell lymphoma with CD20+ tumor cells. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive medications, there are specific guidelines and exceptions, such as a limit on glucocorticoid doses. It's best to discuss your current medications with the trial team to understand any necessary adjustments.

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

Research has shown that epcoritamab has undergone thorough safety testing in humans. In studies involving patients with large B-cell lymphoma, many responded well to the treatment. For example, one study with 148 patients found that 61% had a positive response.

Another study involving patients with aggressive B-cell cancers also reported good results with epcoritamab. The safety profile of epcoritamab appears promising, with consistent results over more than three years of follow-up. This stability and reliability over time offer reassurance to patients considering the treatment.

While every treatment can have side effects, the consistent results suggest that epcoritamab is generally well-tolerated. Ongoing research helps ensure that the benefits of the treatment outweigh the risks for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Epcoritamab is unique because it targets large B-cell lymphoma by using a bispecific antibody approach. Unlike traditional treatments such as chemotherapy or Rituximab, which generally target cancer cells more broadly, epcoritamab is designed to specifically engage both the cancer cells and T-cells, essentially directing the immune system to attack the lymphoma. This targeted mechanism could potentially lead to more effective outcomes with fewer side effects. Researchers are excited about its promise to enhance precision and effectiveness in treating this type of lymphoma.

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 help treat large B-cell lymphoma. In earlier studies, 61% of patients experienced either a reduction or disappearance of their cancer. Specifically, among 148 patients, 38% saw their cancer completely disappear. These results suggest that epcoritamab could be effective for individuals with this type of lymphoma, especially if other treatments have failed. Overall, the treatment has demonstrated potential to significantly reduce cancer in many patients. ^{2 5 6 7 8}

Who Is on the Research Team?

Elise A. Chong, MD

Principal Investigator

Abramson Cancer Center at the University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for individuals with various types of B-cell lymphomas, including Diffuse Large B-Cell Lymphoma. Participants should have a diagnosis that fits the listed conditions and be suitable candidates for CAR T cell therapy.

Inclusion Criteria

Ability and willingness to take proper contraceptive precautions

Pathology report confirming eligible diagnosis

Able to comply with the study protocol, in the investigator's judgment

Exclusion Criteria

I do not have any active infections.

I have had a solid organ transplant.

I cannot or do not want to give consent for treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Epcoritamab Treatment

Participants receive epcoritamab on Cycles 1-3, Days 1, 8, 15, and 22 (once weekly) before CAR T-cell therapy

3 weeks

4 visits (in-person)

CAR T-cell Infusion

Participants undergo CAR T-cell infusion after receiving epcoritamab

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after CAR T-cell infusion

28 days

1 visit (in-person)

Long-term Follow-up

Participants are monitored for progression-free survival, duration of response, and overall survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab

Trial Overview The study is testing the use of epcoritamab in two scenarios: before administering CAR T cells to see if it improves treatment outcomes, and after CAR T cells if there's remaining lymphoma to assess its effectiveness as a follow-up treatment.

How Is the Trial Designed?

Group I: Epcoritamab Experimental Treatment 1 Intervention

Study participants will bridging epcoritamab on Cycles 1-3, Days 1, 8, 15, and 22 (once weekly).

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?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

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, 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, 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]

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]

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]

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

DLBCL Clinical Trial Results - EPKINLY.com EPKINLY helped 61% of patients (90 of 148) achieve complete or partial remission (signs of cancer either disappeared or decreased)

3. 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 demonstrated the feasibility of treating and monitoring patients in an outpatient setting following the first dose of epcoritamab and ...

4. epkinlyhcp.com epkinlyhcp.com/dlbcl/clinical-trial-results

DLBCL Clinical Trial Results - epkinly® hcp EPKINLY delivered an ORR of 61%, with 38% of patients achieving a deep response of CR 1. 61% of patients had a response (n=90/148; 95% CI, 53-69).

5. 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 ... Currently, epcoritamab is approved for R/R DLBCL after two or more prior lines of systemic therapy and is being investigated for use in earlier ...

6. epkinly.com epkinly.com/clinical-trial-results

Clinical Trial Results - EPKINLY® (epcoritamab-bysp) DLBCL: In a clinical study of 148 patients receiving EPKINLY, 61% (90 patients) achieved remission: complete remission in 38% (56 patients) and partial ...

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

Efficacy and safety of epcoritamab in Japanese patients ... Conclusions: With > 3 years of follow-up, epcoritamab treatment has consistently shown durable responses and high rates of MRD negativity in ...

8. 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, ...