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

Trial Summary

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.

What data supports the effectiveness of the drug ibrutinib for treating non-Hodgkin's lymphoma?

Ibrutinib has shown effectiveness in treating certain types of non-Hodgkin's lymphoma, such as mantle cell lymphoma and chronic lymphocytic leukemia, with a significant response rate and improved survival outcomes. It is well-tolerated and has become an important option for patients with these conditions. ^{1 2 3 4 5}

What is known about the safety of Epcoritamab and Ibrutinib for treating Non-Hodgkin's Lymphoma?

Ibrutinib, used for various blood cancers, generally has an acceptable safety profile, but it can cause side effects like bleeding and heart rhythm problems. There have been reports of serious heart issues, such as ventricular fibrillation, in some patients. Epcoritamab's safety data is not detailed here, but it's important to discuss potential risks with your doctor. ^{1 6 7 8 9}

What makes the drug combination of Epcoritamab and Ibrutinib unique for treating Non-Hodgkin's Lymphoma?

The combination of Epcoritamab and Ibrutinib is unique because it pairs Epcoritamab, a bispecific antibody that targets CD3 and CD20 to engage T-cells in attacking cancer cells, with Ibrutinib, an oral drug that inhibits Bruton's tyrosine kinase (BTK) to disrupt cancer cell signaling. This dual approach may enhance the immune system's ability to fight Non-Hodgkin's Lymphoma more effectively than either drug alone. ^{1 10 11 12 13}

What is the purpose of this trial?

This phase Ib/II trial evaluates the safety, optimal dose, and efficacy of the combination of epcoritamab and ibrutinib in treating patients with aggressive B-cell non-Hodgkin lymphoma that has come back (relapsed) or responded to previous treatment (refractory). Epcoritamab, a bispecific antibody, binds to two different types of receptors (proteins present on the cell surface) at the same time. The two receptors that epcoritamab binds to are called CD3 and CD20. CD3 is found on T cells, which are important cells of the immune system that help fight cancer and infections. CD20 is found on the surface of most types of aggressive B-cell non-Hodgkin lymphoma cells. By binding to both CD3 and CD20, epcoritamab brings the two cells close together so the T cells can fight and kill the lymphoma B cells. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, binds to a protein on B cells, a type of white blood cell from which the lymphoma developed. By doing this it decreases the ability of the lymphoma B cells to survive and grow. Ibrutinib may also improve the health (or fitness) of T cells thus making epcoritamab safer and/or more effective.

Research Team

Yazeed Sawalha

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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.

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

Ability to understand and sign informed consent documents

Exclusion Criteria

Serious medical or psychiatric illnesses

Known allergies to study medications

I have not had a stroke or brain bleed recently.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

CD79B limits response of diffuse large B cell lymphoma to ibrutinib. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Ibrutinib for the treatment of mantle cell lymphoma. [2021]

4. United States 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Imbruvica®▾(ibrutinib) patient support programme for chronic lymphocytic leukaemia and mantle cell lymphoma. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Sudden ventricular fibrillation and death during ibrutinib therapy-A case report. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. [2021]

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

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

9. England 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Ibrutinib as a treatment of hematologic autoimmune disorders in patients with indolent B-cell lymphoma. [2023]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety and efficacy analysis of ibrutinib in 32 patients with CLL and various B-cell lymphomas: real-world data from a single-center study in Turkey. [2022]

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

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

13. Germany pubmed.ncbi.nlm.nih.gov

Ibrutinib. [2021]