Epcoritamab for PTLD

Recruiting at 1 trial location

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Timothy Voorhees

Must not be taking: Steroids, Anti-epileptics

Disqualifiers: CNS involvement, Uncontrolled infection, 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: 4

Duration: Up to 12 cycles (28 days each)

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new treatment called epcoritamab for individuals with post-transplant lymphoproliferative disorder (PTLD) that has not improved with other treatments. Epcoritamab aims to help the immune system target and destroy cancer cells. The trial targets those who have undergone organ transplants and have PTLD that either returned after initial improvement or never responded to other treatments. Participants should have had a transplant, experienced treatment failure with therapies like rituximab, and have a form of PTLD involving B-cells. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that any investigational treatments must be completed at least 4 weeks before starting the study treatment. It's best to discuss your specific medications with the trial team.

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

Previous studies have shown that epcoritamab is generally safe for patients with relapsed or refractory post-transplant lymphoproliferative disorder (PTLD). Safety data suggests that patients tolerated the treatment well. Common side effects include fever, tiredness, and injection site reactions, which are typical and manageable. Although rare, more serious side effects can occur, so monitoring patients throughout the treatment is important. Epcoritamab targets specific proteins on cancer and immune cells, aiding the immune system in fighting the cancer. While the data is promising, research continues to better understand its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for post-transplant lymphoproliferative disorders (PTLD), which often involve chemotherapy or rituximab, epcoritamab offers a novel approach by harnessing the immune system. Epcoritamab is a bispecific antibody that specifically targets CD3 and CD20, engaging T-cells to attack B-cells, which are often cancerous in PTLD. This targeted mechanism is what sets epcoritamab apart, potentially leading to a more precise treatment with fewer side effects compared to traditional therapies. Researchers are excited about its ability to directly engage the immune system, offering hope for better outcomes in PTLD patients.

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

Research suggests that epcoritamab, the treatment under study in this trial, might help treat relapsed or refractory post-transplant lymphoproliferative disorder (PTLD). Epcoritamab is a specialized antibody targeting two proteins: CD3 on T cells and CD20 on B cells, aiding the immune system in identifying and destroying cancer cells. In similar conditions like diffuse large B-cell lymphoma (DLBCL), patients have responded well to epcoritamab. Although specific data for PTLD remains limited, early reports are promising and suggest potential benefits for patients with this challenging condition. ^{1 5 6 7 8}

Who Is on the Research Team?

Timothy J. Voorhees, MD, MSCR

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with PTLD, a type of lymphoma that occurs after organ transplant and has either returned or didn't respond to prior treatments. Participants must have measurable disease and be able to undergo procedures like biopsies and scans.

Inclusion Criteria

My condition did not improve after treatment with rituximab alone or with chemotherapy.

My cancer can be measured and is larger than 1.5 cm or is in my bone marrow.

My condition did not improve after reducing my immune-suppressing medication.

Exclusion Criteria

Pregnant or breastfeeding

Electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant

I do not have any uncontrolled illnesses like heart failure or severe high blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive epcoritamab subcutaneously on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 4-9, and day 1 of each subsequent cycle. Cycles repeat every 28 days for up to 12 cycles.

Up to 12 cycles (28 days each)

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 28 days and then every 3 months for up to 3 years.

Up to 3 years

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab

Trial Overview The trial is testing epcoritamab's safety and effectiveness in treating relapsed/refractory B-cell PTLD. Epcoritamab is a bispecific antibody targeting proteins on T cells and some lymphoma cells, potentially helping the immune system destroy cancer.

How Is the Trial Designed?

Group I: Treatment (epcoritamab) Experimental Treatment 5 Interventions

Patients receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 4-9, and day 1 of each subsequent cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR may continue to receive epcoritamab if disease progression occurs within 6 months. Patients with PR or SD continue to receive epcoritamab in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and blood sample collection throughout the study and may undergo biopsy during screening.

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?

Timothy Voorhees

Lead Sponsor

Trials

3

Recruited

70+

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

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 the Phase II PTLD-2 trial involving 60 adult solid organ transplant recipients with CD20-positive PTLD, rituximab monotherapy was effective, achieving a 94% overall response rate, with a 2-year overall survival rate of 100% in the low-risk group.

The study demonstrated that low-risk patients had a 66% event-free survival rate after treatment with rituximab alone, which was comparable to historical controls, while treatment intensification for very-high-risk patients did not yield improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified risk-stratified sequential treatment (subcutaneous rituximab with or without chemotherapy) in B-cell Post-transplant lymphoproliferative disorder (PTLD) after Solid organ transplantation (SOT): the prospective multicentre phase II PTLD-2 trial. Zimmermann, H., Koenecke, C., Dreyling, MH., et al.[2022]

Rituximab, a humanized monoclonal antibody targeting CD-20, was administered to eight patients with post-transplant lymphoproliferative disorders (PTLD) after solid organ transplants, resulting in complete remission in seven cases without any observed side effects.

The study suggests that Rituximab is an effective treatment for PTLD, allowing for reduced immunosuppression and avoiding the side effects associated with traditional chemotherapy, which should only be used for patients who do not respond to Rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Humanized anti-CD20 monoclonal antibody (Rituximab) treatment for post-transplant lymphoproliferative disorder. Ganne, V., Siddiqi, N., Kamaplath, B., et al.[2019]

In a retrospective analysis of 26 adults with post-transplant lymphoproliferative disorder (PTLD), standard CHOP chemotherapy showed a 65% overall response rate, indicating its potential effectiveness in treating this condition.

The median overall survival was 13.9 months and the median progression-free survival was 42 months, providing important survival data for patients with PTLD who do not respond to reduced immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CHOP-21 for the treatment of post-transplant lymphoproliferative disorders (PTLD) following solid organ transplantation. Choquet, S., Trappe, R., Leblond, V., et al.[2022]

In managing posttransplantation lymphoproliferative disorder (PTLD) in adult solid organ transplant recipients, reducing immunosuppression is a key initial step, and treatment is typically initiated within 4 weeks unless there is significant improvement.

For CD20-positive PTLD, which makes up about 75% of cases, the standard treatment involves sequential therapy with rituximab and CHOP chemotherapy for patients who do not respond to reduced immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EBV and posttransplantation lymphoproliferative disease: what to do? Zimmermann, H., Trappe, RU.[2022]

In a study of 24 patients with post-transplant lymphoproliferative disorder (PTLD), rituximab treatment was associated with a significant increase in overall survival, with a median survival of 64 months compared to just 1-30 months for those not treated with rituximab.

The overall response rate to treatment was 62%, with rituximab showing a higher response rate of 66% compared to 50% for non-rituximab treatments, suggesting that rituximab should be considered as a first-line therapy for PTLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line use of rituximab correlates with increased overall survival in late post-transplant lymphoproliferative disorders: retrospective, single-centre study. Martínez-Calle, N., Alfonso, A., Rifón, J., et al.[2017]

Citations

1. researchgate.net researchgate.net/publication/396902483_Epcoritamab_for_RelapsedRefractory_EBV_Post-Transplant_Lymphoproliferative_Disorder_of_DLBCL-Type

(PDF) Epcoritamab for Relapsed/Refractory EBV+ Post ... Case Report Acknowledging the limited data and extrapolating the evidence from trials in DLBCL, we report a case of R/R PTLD successfully ...

2. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/epcoritamab?pn=1

Clinical Trials Using Epcoritamab - NCI Epcoritamab for the Treatment of Relapsed or Refractory Post Transplant Lymphoproliferative Disorders. Status: Active. Location: 2 locations. Epcoritamab for ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12552892/

Epcoritamab for Relapsed/Refractory EBV+ Post‐ ... These outcomes appear similar to those of patients in the CAR‐T clinical trials [6]. Our patient became progressively unfit with refractory ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06672705

Study Details | NCT06672705 | Epcoritamab for the ... This phase Ib trial tests the safety and effectiveness of epcoritamab in treating patients with post-transplant lymphoproliferative disorder (PTLD) that has ...

5. delta.larvol.com delta.larvol.com/NewsItem/NewsItemID/4f92b136-b03f-43aa-acf2-fc4fc2eba7bc/Epcoritamab+for+Relapsed%202fRefractory+EBV%202b+Post-Transplant+Lymphoproliferative+Disorder+of+DLBCL-Type.

Epcoritamab for Relapsed/Refractory EBV+ Post- ... Case report: Acknowledging the limited data and extrapolating the evidence from trials in DLBCL, we report a case of R/R PTLD successfully ...

6. modahealth.com modahealth.com/-/media/modahealth/shared/medical-necessity-criteria/Epkinly.pdf

Epkinly® (epcoritamab-bysp) Mosunetuzumab Monotherapy Demonstrates Durable. Efficacy with a Manageable Safety Profile in Patients with Relapsed/Refractory Follicular.

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

EPKINLY (epcoritamab-bysp) injection - accessdata.fda.gov The recommended dosage schedule for EPKINLY is provided in Table 1. Administer EPKINLY in 28-day cycles until disease progression or unacceptable toxicity.

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

Tepkinly, INN-epcoritamab - European Medicines Agency No evidence of ADA impact on pharmacokinetics, efficacy or safety was observed, however, data are still limited. Neutralising antibodies were not evaluated.