Epcoritamab for Lymphoma

Recruiting at 96 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

184 Participants Needed

Trial Summary

What is the purpose of this trial?

B-cell Lymphoma is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). Classic Follicular Lymphoma is a slow-growing type of non-Hodgkin lymphoma. The purpose of this study is to assess the safety of epcoritamab in adult participants in relapsed or refractory (R/R) diffuse large b-cell lymphoma (DLBCL) who have received at least 1 prior line of systemic antilymphoma therapy including at least 1 anti-CD20 monoclonal antibody-containing therapy or R/R classic follicular lymphoma (cFL). Adverse events will be assessed. Epcoritamab is an investigational drug being developed for the treatment of R/R DLBCL and R/R cFL. Study doctors will assess participants in a monotherapy treatment arm of epcoritamab. Participants will receive escalating doses of epcoritamab, until full dose is achieved. Approximately 184 adult participants with R/R DLBCL and R/R cFL will be enrolled in the study in approximately 80 sites in the United States of America. Participants will receive escalating doses of subcutaneous epcoritamab, until full dose is achieved, in 28-day cycles. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

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.

What data supports the idea that Epcoritamab for Lymphoma is an effective treatment?

The available research shows that Epcoritamab is effective for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In a study, 55.6% of patients showed an overall response, and 44.4% achieved a complete response, meaning their cancer was no longer detectable. These results are promising, especially for patients who have already tried other treatments without success. Additionally, Epcoritamab has shown strong anti-tumor activity in various types of B-cell non-Hodgkin lymphoma, even in patients who did not respond to previous treatments. This suggests that Epcoritamab could be a valuable option for those with limited alternatives. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Epcoritamab for treating lymphoma?

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

What safety data is available for Epcoritamab in treating lymphoma?

The provided research does not contain specific safety data for Epcoritamab or its other names (Epkinly, Tepkinly, epcoritamab-bysp). The studies focus on other treatments for lymphoma, such as Loncastuximab tesirine, Pembrolizumab with Vorinostat, CAR T-cell therapies, and immune checkpoint inhibitors. To find safety data for Epcoritamab, one would need to look for clinical trials or studies specifically evaluating Epcoritamab or its related names. ^{6 7 8 9 10}

Is the drug Epcoritamab a promising treatment for Lymphoma?

Yes, Epcoritamab is a promising drug for treating Lymphoma. It has shown strong anti-tumor activity, especially in patients with relapsed or hard-to-treat forms of the disease. It works by helping the body's immune cells target and destroy cancer cells. Epcoritamab has been approved for use in the USA and has received positive feedback in Europe, with ongoing studies worldwide. ^{1 2 3 4 5}

What makes the drug Epcoritamab unique for treating 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 (through a vein). This drug is particularly promising for patients with relapsed or refractory diffuse large B-cell lymphoma who have not responded to other treatments. ^{1 2 3 4 5}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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, 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, 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]

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]

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]

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]

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]

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]

References

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

Epcoritamab: First Approval. [2023]

2. 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]

3. 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]

4. 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]

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]

7. 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]

8. United States 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. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitor-Related Cytokine Release Syndrome: Analysis of WHO Global Pharmacovigilance Database. [2020]