Study of the Adverse Events and Change in Disease State of Pediatric Participants (and Young Adults Between the Ages of 18-25) With Relapsed/Refractory Aggressive Mature B-cell Neoplasms Receiving Subcutaneous (SC) Injections of Epcoritamab

Study Overview
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Brief Summary
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The most common types of mature B-cell lymphomas (MBLs) in children are Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). Initial treatment cures 90% - 95% of children with these malignancies, leaving a very small population of relapsed/refractory disease with a poor prognosis. The purpose of this study is to assess the safety and tolerability of epcoritamab in pediatric participants with relapsed/refractory aggressive mature B-cell neoplasms and young adult participants with Burkitt's or Burkitt-like lymphoma/leukemia. Adverse events and change in disease activity will be assessed. Epcoritamab is an investigational drug being developed for the treatment of relapsed/refractory aggressive mature B-cell neoplasms. Participants will receive subcutaneous (SC) of epcoritamab. Approximately 15 pediatric participants with a diagnosis of relapsed/refractory aggressive mature B-cell neoplasms and and young adult participants, ages of 18-25, with a diagnosis of Burkitt's or Burkitt-like lymphoma/leukemia will be enrolled at 50 sites globally. Participants will receive subcutaneous epcoritamab in 28-day cycles. Participants will be followed for a minimum of 3 years after enrollment. 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.

Official Title
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A Single Arm, Open-Label, Phase 1b Trial of Epcoritamab in Pediatric Patients With Relapsed/Refractory Aggressive Mature B-cell Neoplasms

Conditions
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Non-hodgkin Lymphoma

Intervention / Treatment
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* Drug: Epcoritamab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants >= 1 and < 18 years old at time of primary diagnosis with Burkitt's or Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma (DLBCL), or other aggressive mature (CD20+) B-cell lymphomas. Participants up to 25 years of age with Burkitt's or Burkitt-like lymphoma/leukemia are also eligible. Disease pathologically confirmed (tumor tissue) by local testing. Relapsed or primary refractory disease meeting any of the following criteria: Progressive disease at any time during second-line chemoimmunotherapy (CIT). Best response of stable disease (SD) after a minimum of 2 cycles of second-line CIT. Best response of partial response (PR) after a minimum of 3 cycles of second-line CIT. Complete Response (CR) after a minimum of 3 cycles of second-line CIT therapy but unfit or ineligible for consolidation with cell therapy. Not in CR and unable to initiate or tolerate (i.e., must discontinue) second-line CIT. Have received cell therapy (allogeneic or autologous transplant or chimeric antigen receptor T-cell (CAR-T) therapy) as consolidation but have not obtained or maintained a CR. Recovery from toxic effects of prior chemoimmunotherapy. Performance status by Lansky (< 16 years old at evaluation) or Karnofsky (>= 16 years old at evaluation) score >= 50 or Eastern Cooperative Oncology Group (ECOG) score <= 2 . Adequate bone marrow, hepatic, and renal function. Exclusion Criteria: Known central nervous system (CNS) involvement by lymphoma at screening as confirmed by screening magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET) brain scans (participants with evidence of CNS disease only in the cerebrospinal fluid (CSF) will be eligible). Other malignancy requiring therapy. Currently receiving anti-cancer therapy, including chemotherapy (excluding intrathecal therapy), radiotherapy, small molecules, monoclonal antibodies, cell therapy, or other investigational agents.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epcoritamab<br>Participants will receive subcutaneous (SC) epcoritamab in 28 day cycles. | Drug: Epcoritamab<br>* Subcutaneous Injection (SC)<br>* Other names: ABBV-GMAB-3013;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AE) | An AE 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. | Up to Approximately 3 Years | 
| Maximum Observed Concentration (Cmax) | Maximum observed concentration. | Up to Approximately Week 37 | 
| Area Under the Concentration Versus Time Curve (AUC) from Time 0 to Time of Last Measurable Concentration within the Dosing Interval (AUCtau) | AUC from time 0 to time of last measurable concentration within the dosing interval. | Up to Approximately Week 37 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve Complete Response (CR) | CR is defined per the International Pediatric Non-Hodgkin Lymphoma Response Criteria as computed tomography (CT) or magnetic resonance imaging (MRI) reveals no residual disease or new lesions; Resected residual mass that is pathologically (morphologically) negative for disease (detection of disease with more sensitive techniques); bone marrow (BM) and cerebrospinal fluid (CSF) morphologically free of disease (detection of disease with more sensitive techniques). | Up to Approximately 1 Year | 
| Number of Participants with Event-free survival (EFS) | EFS will be defined as the number of days from screening to the date of disease progression, treatment failure, or death from any cause. | Up to Approximately 3 Years | 
| Number of Participants who Achieve Overall Survival (OS) | OS will be defined as the number of days from screening to the date of death from any cause. | Up to Approximately 3 Years | 
| Rate of Initiation of Stem Cell Transplantation or Chimeric Antigen Receptor T-cell (CAR-T) Therapy | Rate of initiation of stem cell transplantation or CAR-T therapy. | Up to Approximately 1 Year | 
| Percentage of Participants Achieving Overall Response (OR) | OR is assessed as the percentage of participants with an overall response. | Up to Approximately 1 Year | 
| Duration of response (DOR) | DOR is defined as the time between the date of first response to the date of the first documented tumor progression or death due to any cause, whichever comes first. | Up to Approximately 1 Year | 
| Duration of CR (DOCR) | DOCR is defined as the time between the date of first CR to the date of the first documented tumor progression or death due to any cause, whichever comes first. | Up to Approximately 1 Year | 
| Percentage of Participants Achieving Immunogenicity | Immunogenicity is defined the percentage of participants with ADA and neutralizing anti-drug antibodies (nAb). | Up to Approximately Week 37 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-hodgkin Lymphoma, ABBV-GMAB-3013, Epcoritamab, Burkitt's or Burkitt-like Lymphoma/Leukemia, Diffuse Large B-cell Lymphoma, Aggressive Mature (CD20+) B-cell Lymphoma, Cancer, Relapsed/Refractory Aggressive Mature B-cell Neoplasms, EPCORE