Epcoritamab for Marginal Zone Lymphoma

Overseen By Izidore Lossos, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Izidore Lossos, MD

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: DLBCL transformation, CNS lymphoma, 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: 12 months

25 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 determine its effectiveness for Marginal Zone Lymphoma (MZL), a type of blood cancer. Researchers aim to assess Epcoritamab's efficacy in treating different MZL subtypes, including Extranodal, Nodal, and Splenic forms. Individuals diagnosed with MZL who have not received previous systemic treatment might be suitable candidates, particularly if they exhibit symptoms like enlarged lymph nodes or related issues. Participants will receive Epcoritamab over 12 cycles, each lasting 28 days, with the potential to remain in the study for up to three years. As a Phase 2 trial, this study measures Epcoritamab's effectiveness in an initial, smaller group, allowing participants to contribute to significant research.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it does mention that treatment with systemic immunosuppressive medications should be stopped 2 weeks before starting the trial, and corticosteroids should be reduced to a dose level of 20 mg/day or less within 7 days of starting the trial.

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

Research has shown that Epcoritamab has been tested for safety in people with various types of lymphomas. In one study involving patients whose follicular lymphoma returned or did not respond to treatment, Epcoritamab caused some common side effects. These included cytokine release syndrome (CRS, a reaction that can cause fever and inflammation) in about 49.6% of patients, low white blood cell count in 28%, fever in 23.5%, and tiredness in 22.9%.

Overall, studies indicate that Epcoritamab is generally safe, but like any treatment, it can have side effects. These findings suggest that while Epcoritamab is usually well-tolerated, patients should be aware of and monitor for these side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for marginal zone lymphoma, which typically involve chemotherapy, immunotherapy, or targeted therapies like rituximab, Epcoritamab offers a fresh approach by harnessing the power of bispecific antibodies. This treatment is designed to simultaneously bind to CD3 on T-cells and CD20 on B-cells, effectively directing the body's immune system to attack the cancer cells more precisely. Researchers are excited about Epcoritamab because it potentially offers a more targeted and efficient way to eliminate cancerous cells, which could lead to better outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that Epcoritamab might be an effective treatment for Marginal Zone Lymphoma?

Research has shown that Epcoritamab holds promise for treating certain types of lymphoma. In one study, Epcoritamab helped 82% of patients with follicular lymphoma, a type of non-Hodgkin lymphoma, respond to treatment. Another study found that when combined with other treatments, Epcoritamab helped all patients with a different type of lymphoma called DLBCL respond. This trial will evaluate Epcoritamab for treating Marginal Zone Lymphoma (MZL). Although data specifically for MZL is limited, the strong results in similar conditions offer hope for its potential effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Izidore Lossos, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for patients with a diagnosis of Marginal Zone Lymphoma (MZL), which includes different subtypes like Splenic, MALT, and Nodal MZL. Specific eligibility criteria are not provided.

Inclusion Criteria

Ability to comply with the trial protocol

Able and willing to sign the informed consent form (ICF)

I have a specific type of marginal zone lymphoma.

Exclusion Criteria

My condition has progressed to diffuse large B-cell lymphoma.

I have had brain lymphoma or cancer spread to the lining of my brain.

I am currently being treated for a long-term or active infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 12 cycles of Epcoritamab therapy, each cycle lasting 28 days

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab

Trial Overview The study is testing the effectiveness of Epcoritamab in treating newly diagnosed patients with Marginal Zone Lymphoma. It aims to determine if this investigational treatment can benefit those affected by MZL.

How Is the Trial Designed?

Group I: Epcoritamab Group Experimental Treatment 1 Intervention

Participants will receive up to 12 cycles of Epcoritamab therapy, each cycle lasting 28 days. Total participation is up to 3 years.

Who Is Running the Clinical Trial?

Izidore Lossos, MD

Lead Sponsor

Trials

2

Recruited

60+

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

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 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]

Marginal zone lymphoma (MZL) is often overlooked in clinical trials that focus on other types of indolent lymphomas, highlighting the need for more targeted research.

The study suggests that disease progression within 24 months is linked to worse outcomes in MZL patients, indicating that future research should evaluate the effectiveness of new treatments specifically for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A roadmap for clinical trial design in marginal zone lymphoma. Alderuccio, JP., Habermann, T., Kuker, R., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06796998

Study Details | NCT06796998 | Epcoritamab in Patients ... The purpose of this study is to assess if an investigational treatment of Epcoritamab will be beneficial for patients with Marginal Zone Lymphoma (MZL).

2. ashpublications.org ashpublications.org/blood/article/145/15/1621/535030/Epcoritamab-plus-GemOx-in-transplant-ineligible

Epcoritamab plus GemOx in transplant-ineligible relapsed ... In recently published data, R-GemOx treatment resulted in a median PFS of 3.6 months and a median OS of 12.9 months.4. Current outcomes are ...

3. ajmc.com ajmc.com/view/topline-results-show-epcoritamab-offers-82-response-rate-in-r-r-follicular-lymphoma

Topline Results Show Epcoritamab Offers 82% Response ... Results from the phase 1/2 EPCORE-NHL-1 clinical trial show that epcoritamab produced an 82% overall response rate (ORR) for patients with ...

4. onclive.com onclive.com/view/fixed-duration-epcoritamab-plus-pola-r-chp-demonstrates-durable-efficacy-in-first-line-dlbcl

Fixed-Duration Epcoritamab Plus Pola-R-CHP ... Epcoritamab plus pola-R-CHP achieved a 100% overall response rate in DLBCL, with a 97% complete response rate and durable responses. The regimen ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10850340/

Advances in the treatment of relapsed/refractory marginal ... Firstly, 20% of patients experience disease progression within 24 months of initial treatment (POD24), with a median survival of only 3-5 years (8). Secondly, 5 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06796998

Study Details | NCT06796998 | Epcoritamab in Patients ... The purpose of this study is to assess if an investigational treatment of Epcoritamab will be beneficial for patients with Marginal Zone Lymphoma (MZL).

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/761324Orig1s000MultidisciplineR.pdf

761324Orig1s000 - accessdata.fda.gov Conduct an integrated safety analysis of data from patients with large B-cell lymphoma and other lymphoid malignancies to further ...

8. onclive.com onclive.com/view/epcoritamab-elicits-an-orr-of-82-in-relapsed-refractory-follicular-lymphoma

Epcoritamab Elicits an ORR of 82% in Relapsed ... - OncLive Safety data in this group showed that the most common any-grade AEs were CRS (49.6%), neutropenia (28%), pyrexia (23.5%), and fatigue (22.9%).

9. targetedonc.com targetedonc.com/view/epcoritamab-for-r-r-b-cell-non-hodgkin-lymphoma-proves-safe-effective

Epcoritamab for R/R B-Cell Non-Hodgkin Lymphoma ... The agent proves safe with preliminary antitumor benefit, according to results of a phase 1/2 study published in The Lancet.

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.TPS7569

Phase 3 trial (GCT3013-05) of epcoritamab versus ... Phase 3 trial (GCT3013-05) of epcoritamab versus standard of care in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).