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

Trial Summary

What is the purpose of this trial?

This study investigates the feasibility and efficacy of epcoritamab treatment before CAR T cells. This study also investigates if, when patients have residual lymphoma after CAR T cells, epcoritamab can help to effectively treat that lymphoma.

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.

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

Epcoritamab has shown strong anti-tumor activity in patients with relapsed or refractory large B-cell lymphoma, with response rates of 55.6% and complete response rates of 44.4% in a clinical trial. It works by activating the body's T-cells to target and kill cancerous B-cells, even in patients who have not responded to previous treatments. ^{1 2 3 4 5}

Is Epcoritamab safe for humans?

Epcoritamab has been tested in patients with relapsed or refractory large 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 2 4 5 6}

How is the drug Epcoritamab different from other treatments for 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 who have relapsed or are resistant to other treatments, as it can work even if previous CD20-targeted therapies have failed. ^{1 2 3 4 5}

Research Team

Elise A. Chong, MD

Principal Investigator

Abramson Cancer Center at the University of Pennsylvania

Eligibility Criteria

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

I can give my consent or have someone who can legally do it for me.

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

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

Treatment Details

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.

Participant Groups

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

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]

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]

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]

6. England pubmed.ncbi.nlm.nih.gov

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