A Study to Evaluate Adverse Events of Subcutaneous (SC) Epcoritamab Administered in the Outpatient Setting in Adult Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Classic Follicular Lymphoma
Purpose
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.
Conditions
- Diffuse Large B-Cell Lymphoma
- Classic Follicular Lymphoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Life expectancy >3 months on standard of care (SOC) treatment. - Meets the following disease activity criteria: -- Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): - Documented CD20+ mature B-cell neoplasm according to the the 5th edition of World Health Organization (WHO) classification of Haematolymphoid Tumours, based on most recent representative pathology report; - Diffuse large B-cell lymphoma, not otherwise specified (NOS) (de novo or transformed from follicular lymphoma (FL) or Marginal Zone Lymphoma [MZL]); - High-grade B-cell Lymphoma including "double-hit" or "triple-hit" DLBCL (technically classified in WHO 2022 or 2016 as high-grade B-cell lymphoma [HGBCL], with MYC and BCL2 and/or BCL6 translocations). - Follicular large B-cell lymphoma (FLBL, formerly FL grade 3B); - Relapsed or refractory disease and previously treated with at least 1 prior systemic antineoplastic therapies including at least 1 anti-CD20 monoclonal antibody-containing therapy; Note: Relapsed disease is defined as disease that previously responded to therapy but progressed >= 6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy, failed to achieve an objective response to prior therapy, or progressed within 6 months after completion of therapy (including maintenance therapy). - Either failed prior autologous hematopoietic stem cell transplantation (HSCT), or ineligible for autologous HSCT including but not limited to age, Eastern Cooperative Oncology Group (ECOG) performance status, participant decision, comorbidities and/or insufficient response to prior treatment. - R/R Follicular Lymphoma: - Documented CD20+ mature B-cell neoplasm according to the 5th edition of WHO classification of Haematolymphoid Tumours, based on representative pathology report; --- Classic FL (cFL) (previously FL grade 1, 2, or 3a) without clinical or pathological evidence of transformation; - Relapsed or refractory disease and previously treated with at least 2 prior lines of systemic antineoplastic therapies including at least 1 anti-CD20 monoclonal antibody containing therapy; Note: Relapsed disease is defined as disease that previously responded to therapy but progressed >= 6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy, failed to achieve an objective response to prior therapy, or progressed within 6 months after completion of therapy (including maintenance therapy). - Previously treated with an alkylating agent or lenalidomide; - Relapsed or refractory to the last prior line therapy. Previous lymphoma therapy is defined as 1 of the following: At least 2 months of single-agent therapy, at least 2 consecutive cycles of combination therapy, autologous HSCT, immunomodulatory therapy, or radioimmunotherapy. - Has at least one target lesion defined as: - >= 1 measurable nodal lesion (long axis > 1.5 cm) and/or >= 1 measurable extranodal lesion (long axis > 1.0 cm) on CT (or MRI) AND - FDG PET scan demonstrating positive lesion(s) compatible with CT (or MRI) defined anatomical tumor sites. - Must have ECOG performance status 0 - 2. - Must have acceptable organ (renal, liver, and hematologic) function within the screening period prior to the first dose of study drug: - Absolute neutrophil count (ANC) >= 1.0 × 10^9/L (growth factor support allowed in case of bone marrow involvement, but participant must have not received growth factor within 14 days prior to screening lab collection); - Hemoglobin >= 8.0 g/dL (RBC transfusions permitted, but participants must not have received blood transfusions within 7 days prior to Screening lab collection); - Platelet count >= 75 × 10^9/L, or >= 50 × 10^9/L in the presence of bone marrow involvement or splenomegaly (platelet transfusions are permitted, but participants must not have received blood transfusions within 7 days prior to Screening lab collection); - International normalized ratio (INR) (or Prothrombin Time [PT]) and aPTT <= 1.5 × upper limit of normal (ULN), unless receiving anticoagulation - Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) <= 3.0 × upper limit of normal (ULN); unless due to hepatic involvement of disease or non-hepatic origin. For participants with hepatic involvement of disease, serum AST and serum ALT <= 5.0 × ULN - Direct bilirubin <= 2 × ULN; - Estimated creatine clearance (CrCl) as calculated by Cockcroft-Gault Formula >= 45 mL/min, or estimated glomerular filtration rate (eGFR) as calculated by Modification of Diet in Renal Disease [MDRD] equation >= 45 mL/min; - Lymphocyte count < 5 × 10^9/L.
Exclusion Criteria
- Have a primary central nervous system (CNS) lymphoma or known CNS involvement by lymphoma including leptomeningeal disease, at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) and, if clinically indicated, by lumbar puncture. - Uncontrolled Human Immunodeficiency Virus (HIV) infection. HIV viral load that is undetectable and controlled with medication for at least 1 year prior to enrollment is allowed. Note: If participant has no history of HIV infection, HIV testing does not need to be conducted at screening unless it is required per local guidelines or institutional standards.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Main Cohort: Epcoritamab Diffuse Large B-Cell Lymphoma (DLBCL) |
Participants with relapsed or refractory (R/R) DLBCL will receive subcutaneous (SC) epcoritamab in 28 day cycles. |
|
|
Experimental Main Cohort: Epcoritamab Classic Follicular Lymphoma (cFL) |
Participants with R/R cFL will receive SC epcoritamab in 28 day cycles. |
|
|
Experimental Diversity Enriched Cohort: Epcoritamab DLBCL |
Participants with R/R DLBCL will receive SC epcoritamab in 28 day cycles. |
|
|
Experimental Diversity Enriched Cohort: Epcoritamab cFL |
Participants with R/R cFL will receive SC epcoritamab in 28 day cycles. |
|
Recruiting Locations
Vanderbilt University Medical Center /ID# 260953
Nashville, Tennessee 37232
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Genmab