Epcoritamab for Lymphoma

Not currently recruiting at 98 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genmab

Disqualifiers: CNS lymphoma, Uncontrolled HIV, 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: Unknown

Duration: Up to 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of epcoritamab, a new drug for individuals with aggressive B-cell lymphoma, specifically those with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or classic follicular lymphoma (cFL). The trial aims to evaluate the drug's effectiveness and potential side effects. Participants will receive increasing doses of the drug during 28-day cycles, with regular check-ups and tests. This trial may suit those who have previously tried other treatments for their lymphoma but still have active disease. As a Phase 2 trial, it focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, since the trial involves an investigational drug, it's possible that some medications might need to be adjusted. Please consult with the study doctors for specific guidance.

Do I need to stop my current medications to join 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 study doctors to understand how your current medications might interact with the trial treatment.

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

Research has shown that epcoritamab is generally well-tolerated in people with certain types of lymphoma. In earlier studies, serious infections affected about 32% of patients with follicular lymphoma. Another common side effect is cytokine release syndrome (CRS), which can be serious or life-threatening. CRS occurs when the immune system overreacts to the treatment.

The FDA has already approved epcoritamab for treating certain types of lymphoma that have returned or did not respond to previous treatments. This approval suggests that, despite the risks, the benefits of the drug may outweigh them for many patients. Participants considering joining a trial should know that careful monitoring and medical check-ups help manage these side effects. ^{1 2 3 4 5}

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

Researchers are excited about epcoritamab for treating lymphoma because it offers a new approach compared to traditional therapies like chemotherapy and CAR T-cell therapy. Epcoritamab is a bispecific antibody, meaning it can engage the immune system more directly by simultaneously binding to both cancer cells and immune cells, facilitating a more targeted attack on the tumor. Additionally, it is administered subcutaneously, which can be more convenient and potentially less invasive than intravenous treatments, improving patient experience. This innovative mechanism and delivery method distinguish epcoritamab from existing options and hold promise for more effective treatment of both classic follicular lymphoma and diffuse large B-cell lymphoma.

What evidence suggests that epcoritamab might be an effective treatment for lymphoma?

Research shows that epcoritamab holds promise for treating classic follicular lymphoma (cFL) and diffuse large B-cell lymphoma (DLBCL). In this trial, participants with relapsed or refractory cFL will receive epcoritamab. Studies have shown that 82% of patients responded to the treatment, and 60% achieved complete remission, with no signs of cancer detected. Similarly, participants with relapsed or refractory DLBCL will also receive epcoritamab. Some studies have indicated that it produces lasting positive effects, outperforming other treatments. These findings suggest that epcoritamab could effectively manage these challenging types of lymphoma, offering hope to those whose cancer has returned or not responded to other treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with relapsed or refractory Diffuse Large B-Cell Lymphoma or Follicular Lymphoma, who have had at least two prior treatments including an anti-CD20 therapy. Participants must have adequate organ function and a performance status showing they can carry out daily activities with ease to moderate difficulty.

Inclusion Criteria

My condition has not improved after two cancer treatments, including one with anti-CD20.

My lymphoma shows up on scans and has at least one large tumor.

My organs are working well.

Exclusion Criteria

My cancer has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of subcutaneous epcoritamab in 28-day cycles until full dose is achieved

Up to 3 months

Regular visits at an approved institution

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab

Trial Overview The trial is testing Epcoritamab, an experimental drug for certain aggressive lymphomas. Patients will receive increasing doses of the drug through skin injections in cycles lasting 28 days each, to determine its safety and monitor any adverse effects.

How Is the Trial Designed?

Group I: Main Cohort: Epcoritamab Diffuse Large B-Cell Lymphoma (DLBCL) Experimental Treatment 1 Intervention

Participants with relapsed or refractory (R/R) DLBCL will receive subcutaneous (SC) epcoritamab in 28 day cycles.

Group II: Main Cohort: Epcoritamab Classic Follicular Lymphoma (cFL) Experimental Treatment 1 Intervention

Participants with R/R cFL will receive SC epcoritamab in 28 day cycles.

Group III: Diversity Enriched Cohort: Epcoritamab cFL Experimental Treatment 1 Intervention

Participants with R/R cFL will receive SC epcoritamab in 28 day cycles.

Group IV: Diversity Enriched Cohort: Epcoritamab DLBCL Experimental Treatment 1 Intervention

Participants with R/R DLBCL will receive SC epcoritamab in 28 day cycles.

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

In a study of 182 patients with relapsed/refractory large B-cell lymphoma, novel CAR T-cell therapies showed varying efficacy and safety compared to the FDA-approved Yescarta, with some constructs like tandem CD19.CD20.4-1BBζ demonstrating favorable outcomes.

While some experimental CARs had improved safety profiles, they did not consistently outperform Yescarta in terms of progression-free survival, indicating that further research is needed to establish the best treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Innovative Experimental Chimeric Antigen Receptor (CAR) T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL): Matching Adjusted Indirect Comparisons (MAICs) and Systematic Review. Weinstein, B., Muresan, B., Solano, S., et al.[2022]

A review of 58 cases of cytokine release syndrome (CRS) associated with immune checkpoint inhibitors (ICIs) revealed that 74% of cases were linked to anti-PD-1/PD-L1 agents, with melanoma and hematologic malignancies being the most common cancers involved.

CRS typically developed about 4 weeks after starting ICI treatment, and while there were two fatal cases, 60% of patients were recovering at the time of reporting, highlighting the need for clinicians to be aware of CRS as a potential adverse effect of ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database. Ceschi, A., Noseda, R., Palin, K., et al.[2020]

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]

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]

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]

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]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., 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]

Citations

1. epkinlyhcp.com epkinlyhcp.com/fl/clinical-trial-results

FL Clinical Trial Results - EPKINLY® (epcoritamab-bysp) ... 60% CR was observed in EPCORE® NHL-1 1-4. 82% of patients had a response (n equals 104 out of 127; 95% CI, 74 to 88), 60% of patients had a complete response.

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

Clinical Trial Results - EPKINLY® (epcoritamab-bysp) In follicular lymphoma the most common side effects of EPKINLY include injection site reactions, CRS, COVID-19, tiredness, upper respiratory tract ...

3. onclive.com onclive.com/view/epcoritamab-shines-in-third-line-follicular-lymphoma-with-the-potential-to-move-into-earlier-lines

Epcoritamab Shines in Third-Line Follicular Lymphoma ... 80% of patients with relapsed or refractory follicular lymphoma responded to treatment with the bispecific antibody epcoritamab-bysp (Epkinly) in the third- ...

4. targetedonc.com targetedonc.com/view/epcoritamab-combo-shows-benefits-in-phase-3-follicular-lymphoma-moves-toward-fda-approval

Epcoritamab Combo Shows Benefits in Phase 3 Follicular ... Epcoritamab shows promising results in treating relapsed follicular lymphoma, with FDA priority review for a groundbreaking combination therapy.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05409066

NCT05409066 | Study of Subcutaneous Epcoritamab in ... This study will assess how safe and effective epcoritamab is in combination with lenalidomide and rituximab (R2) in treating adult participants with relapsed or ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761324s000lbl.pdf

EPKINLY (epcoritamab-bysp) injection - accessdata.fda.gov EPKINLY is indicated for the treatment of adult patients with relapsed or refractory diffuse large. B-cell lymphoma (DLBCL), not otherwise specified, including ...

7. epkinly.com epkinly.com/

EPKINLY® for 3L+ DLBCL and FL FDA approved for 2 types of lymphoma that returned or didn't respond after 2 or more prior treatments. EPKINLY is approved for the indications below based on ...

8. ema.europa.eu ema.europa.eu/en/documents/product-information/tepkinly-epar-product-information_en.pdf

Tepkinly, INN-epcoritamab - EMA Follicular lymphoma. In study GCT3013-01, serious infections of any grade occurred in 32% (68/215) of patients with follicular lymphoma treated with epcoritamab ...

9. epkinlyhcp.com epkinlyhcp.com/

EPKINLY® (epcoritamab-bysp) for DLBCL and FL - Official ... IMPORTANT SAFETY INFORMATION. BOXED WARNINGS. Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving ...

10. epkinly.com epkinly.com/fl

EPKINLY® for 3L+ Follicular Lymphoma (FL) EPKINLY is approved based on patient response data. Studies are ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and ...