Epcoritamab + Ibrutinib for Non-Hodgkin's Lymphoma

Recruiting at 1 trial location

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Yazeed Sawalha

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: CNS involvement, Cardiovascular conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

38 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 combination of two drugs, epcoritamab and ibrutinib, for treating aggressive B-cell non-Hodgkin lymphoma that has returned or resisted previous treatments. Epcoritamab (also known as Epkinly or Tepkinly) aids the immune system in identifying and destroying cancer cells, while ibrutinib inhibits cancer cell growth. Individuals with aggressive B-cell lymphoma that has relapsed or not responded to at least two other treatments may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop any strong CYP3A inhibitors or inducers for a certain period before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of epcoritamab and ibrutinib is under testing for safety in treating aggressive B-cell non-Hodgkin lymphoma. Epcoritamab aids the immune system in attacking cancer cells, while ibrutinib inhibits cancer cell growth.

In earlier studies, patients generally tolerated this combination well. Common side effects include tiredness, fever, and low blood cell counts, which are usually manageable. More serious side effects, such as infections, have been less common.

Ibrutinib already has FDA approval for other uses, providing some reassurance about its safety. Epcoritamab remains under study but has shown promising safety results in other research.

Since this trial is in the early stages, the main goal is to ensure the treatment's safety and determine the best dose for patients. Researchers closely monitor participants to manage any side effects that might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Epcoritamab and Ibrutinib for treating Non-Hodgkin's Lymphoma because it introduces a novel approach compared to standard treatments like chemotherapy and monoclonal antibodies. Epcoritamab is a bispecific antibody that uniquely targets both CD3 on T-cells and CD20 on B-cells, potentially enhancing the immune system's ability to attack cancer cells. Meanwhile, Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor that disrupts cancer cell signaling, thereby hindering their growth and survival. This combination aims to provide a more targeted and effective treatment, with the potential for improved patient outcomes and fewer side effects than traditional therapies.

What evidence suggests that the combination of epcoritamab and ibrutinib could be effective for non-Hodgkin's lymphoma?

This trial will evaluate the combination of epcoritamab and ibrutinib for treating aggressive B-cell non-Hodgkin lymphoma, particularly when the disease returns or resists other treatments. Epcoritamab aids the immune system in attacking cancer by bringing immune cells and cancer cells together, while ibrutinib directly targets cancer cells to halt their growth and also enhances the immune system. Earlier research showed promising results with this combination, as 61% of patients with high-risk chronic lymphocytic leukemia and 33% of those with follicular lymphoma responded to treatment. These findings offer hope for patients seeking new treatment options for aggressive lymphomas. ^{1 5 6 7 8}

Who Is on the Research Team?

Yazeed Sawalha

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with aggressive B-cell non-Hodgkin lymphoma that has returned or hasn't responded to treatment. Participants should have a type of lymphoma that the drugs used in this study are designed to target.

Inclusion Criteria

My cancer can be measured or shows up on a PET scan.

My liver and kidney tests are normal.

Satisfactory blood counts (ANC ≥ 1,000/mcL, Platelet count ≥ 75,000/mcL, Hemoglobin ≥ 8 g/dL)

Exclusion Criteria

Serious medical or psychiatric illnesses

Known allergies to study medications

I have not had a stroke or brain bleed recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib orally once daily and epcoritamab subcutaneously according to a specified schedule. Treatment repeats every 28 days for up to 6 cycles of ibrutinib and up to 12 cycles of epcoritamab.

48 weeks

Weekly visits during initial cycles, bi-weekly visits in later cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for 2 years, then every 6 months for up to 5 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Ibrutinib

Trial Overview The trial tests epcoritamab combined with ibrutinib on patients. Epcoritamab is an antibody that helps immune cells attack lymphoma, and ibrutinib blocks a protein helping these cancer cells grow.

How Is the Trial Designed?

Group I: Treatment (epcoritamab, ibrutinib) Experimental Treatment 7 Interventions

Patients receive ibrutinib PO QD on days -7 to 28 of cycle 1 and on days 1 to 28 of remaining cycles, as well as epcoritamab SC on days 1, 8, 15 and 22 of cycles 1-3, days 1 and 15 of cycles 4-9, and on day 1 of remaining cycles. Treatment repeats every 28 days for up to 6 cycles of ibrutinib and up to 12 cycles of epcoritamab in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT and PET/CT throughout the study. Patients may also undergo bone marrow aspiration and biopsy on study.

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?

Yazeed Sawalha

Lead Sponsor

Trials

3

Recruited

60+

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

Ibrutinib is a powerful oral medication that effectively treats relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing high response rates and significantly improving survival outcomes, especially in patients with poor prognostic factors like chromosome 17 deletion (del 17p).

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to side effects, making it a promising option for patients with these types of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Kim, ES., Dhillon, S.[2022]

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

The combination of ibrutinib and nivolumab demonstrated an acceptable safety profile in 141 patients with relapsed or refractory B-cell malignancies, with only one dose-limiting toxicity reported, indicating that this treatment approach is generally safe for patients.

Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36% in diffuse large B-cell lymphoma, suggesting that this combination therapy could be effective for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Younes, A., Brody, J., Carpio, C., et al.[2021]

In a phase 1b/2 study involving 61 patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), the combination of ibrutinib and durvalumab showed an overall response rate of 25%, with the highest response in non-GCB DLBCL patients (38%).

The treatment was generally well-tolerated, with common side effects including diarrhea, fatigue, and nausea, and a notable 20% of patients experienced immune-related adverse events, indicating that while the combination therapy is effective, it also carries additional risks compared to single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma. Herrera, AF., Goy, A., Mehta, A., et al.[2021]

Ibrutinib is an effective oral therapy for chronic lymphocytic leukaemia (CLL), small lymphocytic lymphoma, mantle cell lymphoma, and Waldenstrom's macroglobulinaemia, providing a significant alternative to traditional chemotherapy.

The You&i™ support program enhances patient experience by connecting them with nurses for guidance on treatment and side effects, demonstrating positive feedback from both patients and health professionals in a tested NHS hospital setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imbruvica®▾(ibrutinib) patient support programme for chronic lymphocytic leukaemia and mantle cell lymphoma. Murthy, V., Weaving, S., Paneesha, S.[2021]

Ibrutinib, a BTK inhibitor, was found to be well tolerated and effective in treating relapsed or refractory mantle cell lymphoma (MCL), achieving a 68% overall response rate in a phase II study with 560 mg daily dosage.

The median duration of response to ibrutinib was 17.5 months, and it demonstrated lower toxicity compared to traditional chemotherapy, making it a promising option for patients with MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib for the treatment of mantle cell lymphoma. Herrera, AF., Jacobsen, ED.[2021]

A large-scale analysis of 16,196 serious adverse drug reaction reports identified 36 potential safety signals associated with ibrutinib, including ischemic heart diseases and fractures, highlighting the need for careful patient monitoring.

The study found that over half of the reports resulted in hospitalization, indicating that while ibrutinib is a standard treatment for B-cell malignancies, its safety profile requires further investigation to confirm these findings in broader populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. Allouchery, M., Tomowiak, C., Lombard, T., et al.[2021]

Ibrutinib is an effective treatment for chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), showing better outcomes than traditional therapies like chlorambucil and ofatumumab in phase III trials involving elderly and previously-treated patients.

The drug has a good safety profile, although it can cause some adverse effects like bleeding and atrial fibrillation; it is recommended in treatment guidelines for patients with high-risk disease, including those with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. Deeks, ED.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06536049

Study Details | NCT06536049 | Epcoritamab Plus Ibrutinib ... This phase Ib/II trial evaluates the safety, optimal dose, and efficacy of the combination of epcoritamab and ibrutinib in treating patients with aggressive ...

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

Clinical Trials Using Epcoritamab - NCI Clinical Trials Using Epcoritamab. Review the clinical trials studying epcoritamab on this list and use the filters to refine the results by age and location.

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK605546/

Epcoritamab (Epkinly) - NCBI Bookshelf - NIH The results of the EPCORE NHL-1 study suggested no detriment in health-related quality of life (HRQoL). Patients identified a need for additional treatments ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05283720

NCT05283720 | A Study to Evaluate Adverse Events and ... The purpose of this study is to assess the safety and tolerability of epcoritamab in combination with anti-neoplastic agents in adult participants with Non- ...

5. withpower.com withpower.com/trial/phase-2-lymphoma-9-2024-f767f

Epcoritamab + Ibrutinib for Non-Hodgkin's Lymphoma Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36 ...

6. ctsearchsupport.org ctsearchsupport.org/clinical-trials/epcoritamab-plus-ibrutinib-for-the-treatment-of-relapsed-or-refractory-aggressive-b-cell-non-hodgkin-lymphoma

Two drugs, epcoritamab and ibrutinib , to treat B-cell non- ... To find out:The highest dose of epcoritamab and ibrutinib that's safe to giveIf the combination of epcoritamab and ibrutinib is safe and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9431595/

PB2133: ASSESSING SAFETY, TOLERABILITY, AND ... This open-label, global, multicenter study (EPCORE NHL-5) will evaluate subcutaneous administration of epcoritamab in novel combinations with other anti- ...

8. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M22-132

M22-132 A study to evaluate adverse events and change in disease activity of subcutaneous (SC) epcoritamab in combination with oral and intravenous anti-neoplastic ...