Evaluation of Adjuvant WT1 LAMP mRNA DC Immunotherapy and Temozolomide in Post-Surgical Chemoradiation for Newly Diagnosed Glioblastoma Grade IV

The primary objective of this study is to determine the **overall survival (OS)** and **progression-free survival (PFS)** of patients with newly diagnosed **glioblastoma** when autologous Wilms' tumor 1 mRNA-loaded dendritic-cell vaccination is added to adjuvant temozolomide maintenance treatment following (sub)total resection and temozolomide-based chemoradiation. This is clinically relevant as it aims to improve survival outcomes in a patient population with a typically poor prognosis.

Secondary objectives include evaluating the feasibility, safety, and immunogenicity of combining autologous dendritic-cell vaccination with standard adjuvant treatment in these patients. This assessment is crucial for understanding the potential integration of this immunotherapy approach into existing treatment protocols.

The clinical trial involves participants diagnosed with **glioblastoma grade IV**, a severe form of brain cancer. The study population includes both male and female subjects, aged 18 years and older, who have been newly diagnosed with this condition. Participants are required to have undergone total or subtotal resection of the tumor and are expected to start chemoradiation within a specific timeframe following surgical resection. The trial population was selected based on their ability to comply with the protocol and their fitness to undergo various treatments, including leukapheresis, chemoradiation, chemotherapy, and immunotherapy. The study does not provide specific information on the total number of participants, as this data was not disclosed by the sponsor. Participants are expected to have a life expectancy of at least three months and a WHO performance status of 2 or less. The trial includes a vulnerable population, and both genders are represented. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **safety** and **efficacy** of adjuvant dendritic-cell immunotherapy combined with temozolomide in patients with newly diagnosed **glioblastoma**. This is a Phase I/II trial, characterized by a randomized, double-blind, and controlled design. The trial aims to assess the overall survival (OS) and progression-free survival (PFS) of participants when autologous Wilms' tumor 1 mRNA-loaded dendritic-cell vaccination is added to adjuvant temozolomide maintenance treatment following surgical resection and temozolomide-based chemoradiation. The trial is expected to conclude by June 26, 2026, with recruitment having commenced on April 1, 2016.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histologically verified diagnosis of glioblastoma, a life expectancy of at least three months, and a WHO performance status of 2 or less. Following successful screening, participants will proceed to the treatment phase, which includes leukapheresis, chemoradiation, chemotherapy, and immunotherapy. The study involves regular follow-up visits to monitor the administration of the dendritic-cell vaccine and temozolomide, assess adverse events, and evaluate immune responses. The end-of-study visit will occur after the completion of the treatment regimen or upon early termination.

The expected length of participant involvement is up to 37 weeks, corresponding to the maximum treatment period. 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 participant's best interest by the investigator. The primary endpoints of the trial are overall survival and progression-free survival, while secondary endpoints include feasibility, safety, and immunogenicity assessments. The trial's methodology ensures rigorous evaluation of the investigational therapy's impact on glioblastoma treatment outcomes.

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 **intradermal injection**. The active substance, **WT1 LAMP mRNA DC**, is a structurally diverse substance utilized in cell therapy, specifically involving monocyte-derived dendritic cells electroporated with Wilms' Tumor 1 LAMP mRNA. The maximum daily dose and total dose amount for this treatment are both set at 10,000,000 units, with a maximum treatment period of 37 weeks. The administration schedule and participant compliance are closely monitored to ensure adherence to the dosing regimen.

In addition to the experimental treatment, the study includes the use of **temozolomide**, a standard-of-care therapy for patients with newly diagnosed glioblastoma. Temozolomide is administered as an adjuvant maintenance treatment following surgery and chemoradiation. The combination of WT1 LAMP mRNA DC vaccination with temozolomide aims to evaluate the overall survival and progression-free survival of the participants. The dosing schedule for temozolomide follows established clinical guidelines, and participant compliance is monitored throughout the study to ensure accurate assessment of treatment efficacy.

Efficacy in this clinical trial will be assessed using the primary endpoints of **Overall Survival (OS)** and **Progression-Free Survival (PFS)** in patients with newly diagnosed glioblastoma. These endpoints will provide critical data on the survival benefits and disease progression when autologous Wilms' tumor 1 mRNA-loaded dendritic-cell vaccination is added to adjuvant temozolomide maintenance treatment following surgical resection and chemoradiation.

Secondary endpoints will include the feasibility of the treatment regimen, assessed by the number of patients in the intention-to-treat (ITT) population who successfully undergo leukapheresis, produce qualified vaccines, and receive the scheduled dendritic-cell vaccine administrations. Safety will be evaluated based on the frequency of adverse events, scored according to the latest version of the National Cancer Institute Common Terminology Criteria for Adverse Events. Immunogenicity will be assessed through ex vivo immune responses in the immunogenicity population.