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

Phase 2Active Not RecruitingNCT05451810

Genmab184 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

184

Conditions

Diffuse Large B-Cell Lymphoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Percentage of Participants Experiencing Grade 3 or Higher Cytokine Release Syndrome (CRS) Events

Cytokine Release Syndrome events will be graded using American Society for Transplantation and Cellular Therapy (ASTCT), with a higher grade indicating higher severity.

Time frame: Up to 3 Months

Percentage of Participants Experiencing Grade 3 or Higher Immune Cell-Associated Neurotoxicity Syndrome (ICANS) Events

ICANS events will be graded using ASTCT, with a higher grade indicating higher severity.

Time frame: Up to 3 Months

Percentage of Participants Experiencing Grade 3 or Higher Neurotoxicity (Ntox) Events

Ntox is defined as the percentage of participants who developed at least 1 Grade 3 or higher Ntox since the initiation of epcoritamab treatment.

Time frame: Up to 3 Months

Secondary Outcomes

Best Overall Response (BOR) Determined by Lugano 2014 Criteria Per Investigator Assessment

BOR is defined as the percentage of participants who achieved best overall response of complete response (CR) or partial response (PR) determined by Lugano 2014 criteria as assessed by investigators.

Time frame: Up to 3 Months

CR Determined by Lugano 2014 Criteria Per Investigator Assessment

Complete response is defined as the percentage of participants who achieved best overall response of CR determined by Lugano 2014 criteria as assessed by investigator.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Incidence of Treatment-Emergent Adverse Events (TEAEs) by Severity Level

Treatment-emergent events (TEAEs) are defined as any event that began or worsened in severity after the first dose of study drug.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Severity of TEAEs by Severity Level

Treatment-emergent events (TEAEs) are defined as any event that began or worsened in severity after the first dose of study drug.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Incidence of Serious Adverse Events (SAEs) by Severity Level

A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Severity of SAEs by Severity Level

Time frame: Up to 3 Months

Diversity Enriched Cohort: Median Time to Onset of CRS of Grade 3 or Higher

Median time to onset of CRS of Grade 3 or higher.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Median Time to Resolution of CRS of Grade 3 or Higher

Median time to resolution of CRS of Grade 3 or higher.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Median Time to Onset of ICANS of Grade 3 or Higher

Median time to onset of ICANS of Grade 3 or higher.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Median Time to Resolution of ICANS of Grade 3 or Higher

Median time to resolution of ICANS of Grade 3 or higher.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Median Time to Onset of Ntox of Grade 3 or Higher

Median time to onset of Ntox of Grade 3 or higher.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Median Time to Resolution of Ntox of Grade 3 or Higher

Median time to resolution of Ntox of Grade 3 or higher.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Percentage of Participants Experiencing Any Adverse Events (AE)s

An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Percentage of Participants Receiving Various Interventions for the Management of CRS After the First Full Dose of Epcoritamab

Percentage of participants receiving various interventions for the management of CRS after the first full dose of epcoritamab.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Percentage of Participants Receiving Various Interventions for the Management of ICANS After the First Full Dose of Epcoritamab

Percentage of participants receiving various interventions for the management of ICANS after the first full dose of epcoritamab.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Percentage of Participants Receiving Various Interventions for the Management of Ntox After the First Full Dose of Epcoritamab

Percentage of participants receiving various interventions for the management of Ntox after the first full dose of epcoritamab.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Duration of response (DOR)

Duration of response is defined for participants who achieved BOR of CR or PR ('responders'), as the time in months from initial CR/PR to the earliest occurrence of disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Progression-free survival (PFS)

Progression-free survival is defined as the time in months from the first dose of study drug to the earliest occurrence of disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Overall survival (OS)

Overall survival is defined for as the time in months from first dose of epcoritamab to death from any cause.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Time-to-response (TTR)

Time to response is defined for participants who achieved BOR of CR or PR ('responders') determined by Lugano 2014 criteria as assessed by investigator, as the time in months from first dose of study drug to initial CR/PR.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Duration of CR (DOCR)

The duration of complete response is defined for participants who achieved BOR of CR (Complete Responders), as the duration from the first CR response to the earliest date of disease progression determined per Lugano 2014 criteria, as assessed by the investigator, or death, whichever occurs first.

Time frame: Up to 3 Months

Diversity Enriched Cohort: Time to Next Treatment

Time to next treatment is defined as the time from the date of the first dose of study drug to the start of new non-protocol-specified treatment or death from any cause.

Time frame: Up to 3 Months

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

Overview

Conditions

Interventions

Eligibility

Locations (72)

Outcomes

Primary Outcomes

Secondary Outcomes