Phase 1b Open-Label Study of Epcoritamab in Pediatric Patients with Relapsed/Refractory Aggressive Mature B-cell Neoplasms

The primary objectives of this study are to evaluate the **safety** and pharmacokinetic (PK) profile of **epcoritamab** monotherapy in pediatric patients and young adults with relapsed or refractory Burkitt's or Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma (DLBCL), or other aggressive mature (CD20+) B-cell lymphomas. These patients have either failed to achieve remission with re-induction therapy or are unable to undergo further consolidation with cell therapy. Understanding the safety and PK profile is clinically relevant as it informs the potential for **epcoritamab** to be a viable treatment option for this patient population, who have limited therapeutic alternatives.

The secondary objective of the study is to evaluate the preliminary efficacy and immunogenicity of **epcoritamab** monotherapy. This assessment is crucial for determining the therapeutic potential and immune response elicited by the treatment, which could guide future clinical applications and development strategies for **epcoritamab** in treating aggressive B-cell neoplasms.

The clinical trial involves a total of **9 participants** diagnosed with **relapsed/refractory aggressive mature B-cell neoplasms**, including Burkitt's or Burkitt-like lymphoma/leukemia and diffuse large B-cell lymphoma (DLBCL). The study population comprises both male and female subjects, aged between **1 and 18 years**, with an extension up to **25 years** for those diagnosed with Burkitt's or Burkitt-like lymphoma/leukemia. Participants were selected based on their inability to achieve remission with re-induction therapy or their ineligibility for further consolidation with cell therapy. The trial includes a vulnerable population, requiring informed consent from legally authorized representatives for minors. Participants must have a performance status by Lansky or Karnofsky score of at least 50, or an ECOG score of 2 or less, and must demonstrate adequate bone marrow, hepatic, and renal function. The trial does not specify particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **single-arm, open-label, Phase 1b study** to evaluate the safety and pharmacokinetics of **epcoritamab** in pediatric patients with relapsed or refractory aggressive mature B-cell neoplasms. The trial aims to assess the safety and pharmacokinetic profile of epcoritamab monotherapy in patients who have not achieved remission with re-induction therapy or are unable to undergo further consolidation with cell therapy. The study is expected to run from October 4, 2022, to November 27, 2028, with participant involvement lasting until the end of the study or until early termination conditions are met.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease status, and ability to tolerate subcutaneous injections. Follow-up visits will be scheduled to monitor safety, tolerability, and pharmacokinetic parameters, with primary endpoints focusing on adverse events of special interest, including Cytokine Release Syndrome, Immune Cell-Associated Neurotoxicity Syndrome, and Clinical Tumor Lysis Syndrome. Secondary endpoints include complete response per the International Pediatric Non-Hodgkin Lymphoma Response Criteria, event-free survival, overall survival, and other response metrics.

The expected length of participant involvement is contingent upon individual response to treatment and overall health status. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or any situation where continued participation is deemed not in the best interest of the participant by the investigator. The trial will not include incarcerated individuals or those unable to provide informed consent. The study will adhere to ethical guidelines, requiring informed consent from participants or their legally authorized representatives before any study-specific procedures are initiated.

The clinical trial involves the administration of **Epcoritamab (GEN3013)**, a bispecific antibody, as the experimental medication. Epcoritamab is formulated as a **solution for injection** and is administered via the **subcutaneous** route. The active substance, **epcoritamab**, is a protein of other origin, specifically designed for targeting CD20+ B-cell lymphomas. The pharmaceutical form is consistent across all administrations, ensuring uniformity in the delivery of the therapeutic agent. The trial does not specify a pediatric formulation, indicating that the same formulation is used for both pediatric and young adult participants. The dosing schedule and frequency of administration are not detailed in the provided data.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on evaluating the safety and pharmacokinetic profile of Epcoritamab monotherapy in the specified patient population. Participant compliance with the treatment regimen is monitored, although specific methods for compliance monitoring are not described in the available information. The trial is designed to assess the efficacy of Epcoritamab in pediatric patients with relapsed or refractory aggressive mature B-cell neoplasms, including Burkitt's or Burkitt-like lymphoma/leukemia and diffuse large B-cell lymphoma (DLBCL), who have not achieved remission with re-induction therapy or are unable to undergo further consolidation with cell therapy.

The efficacy of the clinical trial involving **epcoritamab** will be assessed through several secondary endpoints. These include the Complete Response (CR) as per the International Pediatric Non-Hodgkin Lymphoma Response Criteria, Event-Free Survival (EFS), Overall Survival (OS), and the rate of initiation of stem cell transplantation or chimeric antigen receptor T-cell (CAR-T) therapy. Additional measures include Overall Response (OR), Duration of Response (DOR), Duration of Complete Response (DOCR), and immunogenicity, which will be evaluated through the presence of anti-drug antibodies (ADA) and neutralizing anti-drug antibodies (nAb).