Trials / Recruiting

RecruitingNCT06536049

Epcoritamab Plus Ibrutinib for the Treatment of Relapsed or Refractory Aggressive B-Cell Non-Hodgkin Lymphoma

Phase Ib/II Trial of Epcoritamab Plus Ibrutinib in Patients With Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma

Status: Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 38 (estimated)

Sponsor: Yazeed Sawalha · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: I. Determine the recommended phase II dose (RP2D) and safety of epcoritamab plus ibrutinib. II. Determine the rate and severity of cytokine release syndrome (CRS). SECONDARY OBJECTIVES: I. Determine the complete response (CR) rate (Lugano 2014) after cycle 12 or the last dose of treatment if stopped earlier. II. Determine the overall response rate (ORR) (CR + partial response \[PR\]) (Lugano 2014), progression-free survival (PFS), duration of response (DOR), and overall survival (OS) of patients treated at the RP2D. III. Determine the best ORR and CR rate (Lugano 2014). EXPLORATORY OBJECTIVES: I. Characterize cytokine profile following ibrutinib and epcoritamab and explore whether levels of cytokine production correlate with both the appearance of CRS and ORR. II. Analyze peripheral blood mononuclear cells collected pre-ibrutinib, pre-epcoritamab, and throughout treatment using spectral flow cytometry to assess the effect of ibrutinib on T-cell numbers and function. III. Examine tumor samples attained before starting treatment and at relapse and explore aspects of the microenvironment that may contribute to epcoritamab failure. IV. Measure circulating tumor deoxyribonucleic acid (DNA) (ctDNA) to correlate its presence with response by positron emission tomography (PET) imaging and track the emergence of treatment-resistant clones. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days -7 to 28 of cycle 1 and on days 1 to 28 of remaining cycles, as well as epcoritamab subcutaneously (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, computed tomography (CT) and PET/CT throughout the study. Patients may also undergo bone marrow aspiration and biopsy on study. After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for up to 5 years.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and biopsy
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and biopsy
PROCEDURE	Computed Tomography	Undergo CT and PET/CT
BIOLOGICAL	Epcoritamab	Given SC
DRUG	Ibrutinib	Given PO
PROCEDURE	Positron Emission Tomography	Undergo PET/CT

Timeline

Start date: 2025-04-02
Primary completion: 2026-12-31
Completion: 2028-12-31
First posted: 2024-08-02
Last updated: 2026-02-19

Locations

2 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06536049. Inclusion in this directory is not an endorsement.