Epcoritamab for B-Cell Lymphoma

(EPCORE™ NHL-1 Trial)

Recruiting at 87 trial locations

Overseen By Genmab Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genmab

Must be taking: Anti-CD20 antibodies

Must not be taking: Steroids, Anti-epileptics

Disqualifiers: CNS lymphoma, Cardiovascular disease, Autoimmune, others

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

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

Compensation: Varies

Number of Visits: 2

666 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get a clear answer.

What data supports the effectiveness of the drug Epcoritamab for B-cell lymphoma?

Epcoritamab has shown strong anti-tumor activity in patients with different types of B-cell lymphoma, including diffuse large B-cell lymphoma, with response rates of over 55% in clinical trials. It works by helping the body's immune cells target and kill cancerous B-cells, even in patients who have not responded to other treatments. ^{1 2 3 4 5}

Is Epcoritamab safe for humans?

Epcoritamab has been tested in patients with B-cell lymphoma and showed a manageable safety profile. Common side effects included cytokine release syndrome (a reaction that can cause fever and low blood pressure), injection-site reactions, infections, and low white blood cell counts, but these were mostly mild and resolved without stopping treatment. ^{1 3 4 5 6}

How is the drug Epcoritamab different from other treatments for 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 different from many other treatments that are given intravenously. It is specifically designed to work even in patients who have not responded to previous CD20-targeted therapies. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this trial is to measure the following in participants with relapsed and/or refractory B-cell lymphoma who receive epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20): * The dose schedule for epcoritamab * The side effects seen with epcoritamab * What the body does with epcoritamab once it is administered * What epcoritamab does to the body once it is administered * How well epcoritamab works against relapsed and/or refractory B-cell lymphoma The trial consists of 3 parts: * a dose-escalation part (Phase 1, first-in-human \[FIH\]) * an expansion part (Phase 2a) * a dose-optimization part (OPT) (Phase 2a) The trial time for each participant depends on which trial part the participant enters: * For the dose-escalation part, each participant will be in the trial for approximately 1 year, which is made up of 21 days of screening, 6 months of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant). * For the expansion and dose-OPT parts, each participant will be in the trial for approximately 1.5 years, which is made up of 21 days of screening, 1 year of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant). Participation in the study will require visits to the sites. During the first month, participants must visit every day or every few days, depending on which trial part the participant enters. After that, participants must visit weekly, every other week, once a month, and once every 2 months, as trial participation ends. All participants will receive active drug, and no participants will be given placebo.

Research Team

Study Official

Principal Investigator

Genmab

Eligibility Criteria

This trial is for adults with various types of B-cell lymphoma that have relapsed or didn't respond to previous treatments, including an anti-CD20 monoclonal antibody. Participants should be in a stable condition (ECOG 0,1,2), have measurable disease and proper kidney and liver function. Those with CNS lymphoma involvement, other cancers, significant heart conditions, immune diseases requiring suppression therapy, recent CAR-T therapy or stem cell transplant are excluded.

Inclusion Criteria

I'm sorry, but I'm unable to understand what "FL" stands for in this context. Could you please provide more information or clarify?

I have been diagnosed with small lymphocytic lymphoma (SLL).

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

Exclusion Criteria

I have previously been treated with a specific experimental drug for my condition.

I have not had CAR-T therapy in the last 30 days.

I am eligible for a high-intensity treatment plan aimed at curing my cancer, followed by stem cell transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

Dose-Escalation

Participants receive epcoritamab to determine the maximum tolerated dose and establish the safety profile

6 months

Daily or every few days for the first month, then weekly

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Expansion

Additional participants are treated with epcoritamab at the recommended Phase 2 dose to further explore safety and efficacy

1 year

Weekly, every other week, once a month, and once every 2 months

Dose-Optimization

Evaluation of alternative priming and intermediate dose regimens of epcoritamab

1 year

Treatment Details

Interventions

• Epcoritamab

Trial Overview Epcoritamab (EPKINLY™/GEN3013) is being tested in this multi-phase trial to determine its safety and effectiveness against B-cell lymphomas. The study includes dose-escalation to find the right amount of drug needed (Phase 1), expansion to treat more patients at that dose (Phase 2a), and optimization to refine dosing further (Phase 2a).

Participant Groups

Group I: Epcoritamab Experimental Treatment 1 Intervention

Epcoritamab will be administered by subcutaneous injections in cycles of 28 days.

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

Findings from Research

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, 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, 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 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]

The combination of pembrolizumab and vorinostat was found to be tolerable in patients with relapsed/refractory B-cell lymphomas, although there were serious adverse events, including one case of Stevens-Johnson syndrome that led to a fatal infection.

The treatment showed promising efficacy, especially in primary mediastinal B-cell lymphoma (PMBL), with a complete response rate of 80% and overall response rate of 80%, while overall response rates for other non-PMBL diffuse large B-cell lymphoma (DLBCL) were lower at 33%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma. Godfrey, J., Mei, M., Chen, L., et al.[2023]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Epcoritamab: First Approval. [2023]

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. Italy pubmed.ncbi.nlm.nih.gov

Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma. [2023]