Evaluation of [18F]AlF-PSMA-11 PET Imaging in Advanced Head and Neck Squamous Cell Carcinoma and Thyroid Carcinoma

The primary objective of this study is to **demonstrate uptake** of [¹⁸F]AlF-PSMA-11 in lesions on PET imaging in patients with advanced head and neck squamous cell carcinoma and thyroid carcinoma. This is clinically relevant as it may provide a novel imaging modality for detecting and evaluating these malignancies, potentially improving diagnostic accuracy and treatment planning.

Secondary objectives include:

• Comparing lesion uptake of [¹⁸F]AlF-PSMA-11 to that of [¹⁸F]FDG on PET, which could offer insights into the relative effectiveness of these imaging agents.
• Comparing lesion uptake of [¹⁸F]AlF-PSMA-11 to that of radioiodine on thyroid scintigraphy, which may help in assessing the utility of [¹⁸F]AlF-PSMA-11 in thyroid cancer imaging.
• Assessing biodistribution and organ-specific dosimetry analysis of [¹⁸F]AlF-PSMA-11 using PET, which is important for understanding the safety and potential radiation exposure associated with this imaging agent.

The clinical trial involves participants diagnosed with **head and neck squamous cell carcinoma** and thyroid carcinoma. The study population includes both male and female subjects aged 18 years and older. Participants are required to be willing and mentally and legally capable of providing written informed consent. They must have at least one measurable lesion of interest of 1.0 cm or greater on medical imaging. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants have a measurable lesion, which is crucial for the study's objective to demonstrate uptake of [¹⁸F]AlF-PSMA-11 in lesions on PET scans.

The clinical trial is designed to evaluate the uptake of **[18F]AlF-PSMA-11** in lesions using PET imaging in patients with advanced **head and neck squamous cell carcinoma** and **thyroid carcinoma**. This is a Phase IV, randomized, double-blind, controlled study, with an estimated duration from July 2023 to November 2026. The trial aims to assess both qualitative and semiquantitative uptake of the radiotracer in lesions and organs, with endpoints measured within 12 months after the last trial-specific intervention for each subject and for the entire trial.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as being 18 years or older, capable of providing informed consent, and having at least one measurable lesion of interest. Following the screening, participants will receive the investigational product, **[18F]PSMA-11**, administered via intravenous injection. The maximum daily dose is 4.4 MBq/kg, with a treatment period limited to one day.

Subsequent follow-up visits will be scheduled to monitor the uptake of the radiotracer and assess any adverse effects. The end-of-study visit will conclude the participant's involvement, which is expected to last up to 12 months post-intervention. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial is not categorized as low intervention, and it is not intended for pediatric populations.

The clinical trial involves the administration of the experimental medication **[18F]PSMA-11**, which is a **solution for injection**. The active substance in this formulation is **gozetotide alf-18**, also known by its synonyms **AL(18F)PSMA-11** and **(AL18F)PSMA-HBED**. This compound is chemically synthesized and is intended for use in the study to demonstrate its uptake in lesions on PET imaging in patients with advanced thyroid and head and neck carcinoma. The medication is administered via **intravenous injection**. The dosing regimen specifies a maximum daily dose of **4.4 MBq/kg** and a maximum total dose of **4.4 MBq/kg**. The treatment period is limited to a single day, ensuring that the administration is concise and controlled.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the investigational product, **[18F]PSMA-11**, to assess its efficacy and safety profile in the specified patient population. Participant compliance with the dosing schedule is monitored through standard clinical trial procedures, ensuring adherence to the protocol and accurate assessment of the investigational product's effects.

Efficacy in this clinical trial will be assessed through the evaluation of **[18F]AlF-PSMA-11** uptake in lesions using PET imaging. The primary endpoint is the qualitative count of lesions with significant **[18F]AlF-PSMA-11** uptake on PET. This endpoint will be measured for each subject within 12 months after the last trial-specific intervention, which includes PET/CT or blood sampling. For the entire trial, all primary endpoints will be measured within 12 months after the overall last trial-specific intervention.

Secondary endpoints include semiquantitative lesion radiotracer **[18F]AlF-PSMA-11** uptake values and semiquantitative organ-level radiotracer uptake values on PET. These secondary endpoints will also be measured within 12 months after the last trial-specific intervention for each subject and for the whole trial. The assessments will utilize PET imaging to determine the uptake values, providing both qualitative and semiquantitative data on the radiotracer's distribution and concentration in lesions and organs.