Evaluation of WT1 LAMP mRNA DC Vaccine as Adjuvant Therapy in Pediatric High-Grade Glioma and Diffuse Intrinsic Pontine Glioma

The primary objective of this study is to evaluate the **feasibility** of producing and administering the WT1-targeted dendritic cell (DC) vaccine in pediatric patients diagnosed with high-grade glioma (HGG) and diffuse intrinsic pontine glioma (DIPG). This evaluation will be conducted either in combination with first-line chemoradiation treatment or as an adjuvant therapy following previous treatments. Additionally, the study aims to investigate the resulting safety profile of this therapeutic approach. The clinical relevance of this objective lies in its potential to enhance treatment options for these aggressive pediatric brain tumors, which currently have limited effective therapies.

Secondary objectives include:

• Assessing indicators of clinical activity of the vaccination in the target patient population.
• Determining the in vivo immunogenicity of the WT1-targeted DC vaccinations.
• Documenting and characterizing changes in both patient- and proxy-reported general and disease-specific quality of life.

The clinical trial involves a study population of pediatric patients diagnosed with **high-grade glioma (HGG)** or **diffuse intrinsic pontine glioma (DIPG)**. The participants are aged between 12 months and less than 18 years, with both male and female subjects included. The trial population is characterized by a vulnerable group, given the serious nature of the medical conditions involved. Participants are required to have a body weight of at least 10 kg and a reasonable life expectancy of 8 weeks or more, as estimated by the treating physician. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The selection criteria include adequate hematological blood values and sufficient recovery from treatment-related toxicities for those who have undergone previous anti-glioma treatments. Lifestyle considerations such as diet and physical activity are not detailed in the available data. The trial aims to evaluate the feasibility of WT1-targeted DC vaccine production and administration, either in combination with first-line chemoradiation treatment or as adjuvant therapy following previous therapies, while investigating the resulting safety profile.

The clinical trial is designed to evaluate the feasibility and safety of **WT1-targeted dendritic cell (DC) vaccine** production and administration in pediatric patients diagnosed with high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). This is a Phase I/II trial, which is not categorized as low intervention, and aims to assess the vaccine's efficacy when used in combination with first-line chemoradiation treatment or as an adjuvant therapy following previous treatments. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The estimated duration of the trial is from October 2021 to September 2025, with participant involvement expected to last up to 40 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and health status. The inclusion criteria require participants to be aged between 12 months and 18 years, with a body weight of at least 10 kg, and a reasonable life expectancy of at least 8 weeks. Following successful screening, participants will proceed to the leukapheresis procedure, which is essential for vaccine production. Subsequent visits will involve the administration of the vaccine via **intradermal injection** and monitoring for adverse events (AEs) and serious adverse events (SAEs). Follow-up visits will be scheduled to assess the safety and immunogenicity of the vaccine, as well as to evaluate clinical activity indicators such as progression-free survival and overall survival.

The end-of-study visit will mark the conclusion of the participant's involvement, during which final assessments of safety, efficacy, and quality of life will be conducted. Participants may be withdrawn from the study early if they experience unacceptable toxicity, fail to comply with the protocol, or if the treating physician deems it necessary for their safety. The primary endpoints of the trial include the feasibility of vaccine production and administration, as well as the safety profile based on the occurrence of AEs and SAEs. Secondary endpoints focus on clinical activity, immunogenicity, and quality of life measures. The trial aims to provide valuable insights into the potential benefits of the WT1-targeted DC vaccine for pediatric patients with HGG and DIPG.

The clinical trial involves the administration of an experimental medication known as **WT1 LAMP mRNA DC**. This investigational product is formulated as a **suspension for injection** and is designed for use in pediatric patients with high-grade glioma and diffuse intrinsic pontine glioma. The active substance, **WT1 LAMP mRNA DC**, is a structurally diverse substance categorized under cell therapy. The therapy involves monocyte-derived dendritic cells that have been electroporated with Wilms' Tumor 1 LAMP mRNA. The medication is administered via **intradermal injection**. The maximum daily dose is set at 10,000,000 units, with a total maximum dose of 10,000,000 units over a treatment period not exceeding 40 days.

In this study, the experimental treatment is evaluated for its feasibility and safety profile when used as an adjuvant therapy or in combination with first-line chemoradiation treatment. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The trial aims to assess the production and administration of the WT1-targeted DC vaccine in the specified patient population.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on the **feasibility** of the WT1-targeted dendritic cell (DC) vaccine production and administration. This includes evaluating the proportion of patients in the intention-to-treat (ITT) population who successfully undergo leukapheresis, achieve successful vaccine production (defined as the production of nine or more vaccines meeting quality control requirements), and complete the study treatment schedule from leukapheresis to the administration of the ninth vaccine. Additionally, the trial will assess the proportion of efficacy-evaluable patients within the ITT population.

Secondary endpoints will include indicators of clinical activity such as best overall response, progression-free survival, and overall survival. Immunogenicity will be evaluated by measuring functional WT1-specific T cell responses and the occurrence of WT1-specific CD8+ T cells. Quality of life assessments will be conducted to understand how patients experience different phases of the study treatment schedule, as well as how patient- and proxy-reported disease-related symptoms and general quality of life evolve over time during the study.