Long-term Safety Evaluation of GD2IL18CART in Patients with Neuroblastoma, Osteosarcoma, Ewing Sarcoma, and Advanced Breast Cancer

The primary objective of this study is to evaluate the long-term **safety** of the treatment with GD2IL18CART in patients diagnosed with **neuroblastoma**, **osteosarcoma**, **Ewing sarcoma**, and **advanced breast cancer**. This is clinically relevant as it aims to ensure that the therapeutic intervention does not pose significant risks to patients over an extended period, which is crucial for the management of these serious conditions.

Secondary objectives include:

• To further assess safety concerning growth and development in pediatric patients, which is important for understanding the impact of the treatment on younger populations.
• To evaluate long-term treatment efficacy by measuring disease progression and survival status over time, as well as the persistence of the transgene. This will provide insights into the durability and effectiveness of the therapy in managing the disease.

The clinical trial involves participants who have previously undergone treatment with **GD2IL18CART** in a primary trial and are now being evaluated for long-term safety. The study population includes both male and female subjects, with an age range encompassing children, adolescents, and adults. The trial does not specifically target a vulnerable population. Participants have been diagnosed with conditions such as **neuroblastoma**, **osteosarcoma**, **Ewing sarcoma**, and **advanced breast cancer**. The sponsor has not provided information regarding the total number of participants. Selection criteria include prior treatment with GD2IL18CART and the provision of informed consent by the patient or caregivers. No specific lifestyle considerations such as diet or physical activity are highlighted in the trial details.

The clinical trial is designed to evaluate the long-term safety of **GD2IL18CART** in patients who have previously undergone treatment with this investigational product. The study is a follow-up of patients treated in a Phase 1 trial and is not categorized as a low-intervention study. The trial will include patients with conditions such as **neuroblastoma**, **osteosarcoma**, **Ewing sarcoma**, and **advanced breast cancer**. The trial is structured as a long-term observational study, with an estimated duration extending until May 31, 2041. Participants will be involved in the study from the recruitment start date of July 4, 2025, until the end of the trial or until they meet criteria for early termination.

Study visits are sequenced to ensure comprehensive monitoring of participants. The inclusion visit, or screening, will confirm eligibility based on prior treatment with GD2IL18CART and informed consent. Follow-up visits will be scheduled to assess primary endpoints, including the percentage of patients experiencing late-onset adverse reactions, serious adverse events, and adverse reactions of special interest. Secondary endpoints will evaluate pediatric growth parameters, relapse rates, survival probabilities, and transgene levels. If transgene levels are undetectable for two consecutive years, further sampling for that patient will cease. The end-of-study visit will conclude the participant's involvement, summarizing all collected data and outcomes.

Participant involvement is expected to last until the trial's conclusion unless early termination criteria are met. Conditions for early termination include withdrawal of consent, significant protocol deviations, or the occurrence of adverse events that necessitate discontinuation. The trial's design ensures rigorous data collection and analysis to achieve its primary objective of assessing long-term safety post-treatment with GD2IL18CART.

The clinical trial involves the administration of the experimental medication **GD2IL18CART**, which is a **Structurally Diverse Substance** used in **Cell therapy**. The pharmaceutical form of GD2IL18CART is an **infusion**, and it is administered through a route categorized as **OTHER USE**. The medication is not a pediatric formulation and is not classified as an orphan drug. The trial aims to evaluate the long-term safety of GD2IL18CART in patients. The specific dosage, frequency of administration, and maximum treatment period are not detailed in the available data.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The trial focuses solely on the administration of GD2IL18CART. Participant compliance monitoring and additional relevant information about drug administration and dosing schedules are not specified in the provided data.

Efficacy in the clinical trial titled "Long-term follow-up of patients treated with GD2IL18CART" will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the percentage of patients experiencing late-onset adverse reactions, serious adverse events, serious adverse reactions, and adverse events of special interest, which include relapse or progression of the underlying disease, life-threatening infections, death due to any cause, and new and secondary malignancies.

Secondary endpoints will include various parameters such as height and weight, Tanner status for pediatric patients, the percentage of patients who relapse or progress since enrollment, and the rate of surviving patients. Additionally, probabilities of overall survival and disease-free survival will be evaluated, along with the duration of response, relapse rate, and time to relapse. The percentage of patients with detectable transgene levels will also be monitored, with further sampling discontinued for patients with negative results over two consecutive years.