Evaluation of 64Cu-DOTA-AE105 PET Imaging for ISUP Grade Classification in Localized, Untreated Prostate Cancer Patients

The primary objective of this phase 2 clinical trial is to assess the robustness of **SUVmax** measurements obtained at a 64Cu DOTA-AE105 dose of 100 MBq, 150 MBq, and 200 MBq in patients with untreated, localized **prostate cancer**. Additionally, the trial aims to determine the discriminative properties of uPAR PET (SUVmax) for the classification of ISUP grades 1 from 2 and ISUP grades 2 from 3 in these patients. This is clinically relevant as it may enhance the non-invasive classification of prostate cancer grades, potentially improving diagnostic accuracy and treatment planning.

Secondary objectives include: - Evaluating the day-to-day variation (within patient reproducibility) of SUVmax at different doses of 64Cu DOTA AE105. - Determining the pharmacokinetics of 64Cu-DOTA-AE105. - Assessing inter-reader and intra-reader variability in SUV calculations and tumor visibility. - Evaluating SUVmax and tumor visibility following a single intravenous injection using different acquisition durations. - Determining the variation between local unblinded and central blinded reads, as well as agreement among local unblinded readers and a consensus from a blinded central read. - Assessing inter-reader and intra-reader variability and agreement in tumor visibility.

The clinical trial involves a total of **28 male participants** diagnosed with **prostate cancer**. The study population consists of individuals within the age range of 18 to 64 years, specifically targeting those with untreated, localized prostate adenocarcinoma. Participants were selected based on pathology-verified prostate adenocarcinoma, with pathology material available for central review, and classified within the International Society of Urological Pathology (ISUP) grades 1 to 3. The trial excludes individuals with clinical suspicion of cancer outside the prostatic bed and requires that any N- and M-staging performed must result in N0 and M0. A prostate biopsy conducted within 1 to 6 months prior to the first planned day of injection of 64Cu-DOTA-AE105 is mandatory, with at least one core being MRI-guided. The trial does not include female subjects or vulnerable populations, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed as an open-label, two-part, phase 2 study to evaluate the safety and diagnostic performance of **uPAR PET imaging** in patients with localized, untreated **prostate cancer**. The trial aims to assess the robustness of SUVmax measurements at various doses of **64Cu-DOTA-AE105** and to determine the discriminative properties of uPAR PET for classifying ISUP grades among patients. The study is expected to commence recruitment on January 1, 2024, and conclude by December 30, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as pathology-verified prostate adenocarcinoma and ISUP grade 1 to 3. The trial will involve multiple follow-up visits to monitor the primary and secondary endpoints, including SUVmax measurements at specified time points post-injection and evaluation of pharmacokinetic parameters. The end-of-study visit will mark the completion of the participant's involvement in the trial.

The expected duration of participant involvement will vary depending on the specific part of the trial they are enrolled in, with the possibility of early termination if any exclusion criteria are met or if adverse events occur. The trial will utilize a **solution for injection** form of the investigational product, administered intravenously. The study's design and procedures are structured to ensure the collection of comprehensive data on the investigational product's safety and diagnostic efficacy in the target patient population.

The clinical trial involves the administration of **64Cu-DOTA-AE105**, a radiopharmaceutical agent used for diagnostic imaging. The experimental medication is provided in the form of a **solution for injection**. The active substance, **64Cu-DOTA-AE105**, is a protein-based compound categorized under "Protein - Other" origin. The pharmaceutical form is a solution specifically designed for intravenous administration. The trial protocol specifies three different dosages: 100 MBq, 150 MBq, and 200 MBq, to be administered intravenously. The frequency of administration is determined by the study protocol, focusing on the evaluation of the robustness of SUVmax measurements in patients with localized, untreated prostate cancer.

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, **64Cu-DOTA-AE105**, to assess its diagnostic performance in non-invasive classification of ISUP grades among the target patient population. Participant compliance with the dosing schedule is monitored through standard clinical trial procedures, ensuring adherence to the protocol and accurate data collection.

Efficacy in this clinical trial will be assessed through the evaluation of the **SUVmax** (Standardized Uptake Value maximum) in PET (Positron Emission Tomography) imaging. The primary endpoints include measuring **SUVmax** at various time points post-injection of the investigational product, 64Cu-DOTA-AE105. In Part 1, **SUVmax** will be measured at 30, 60, and 120 minutes post-injection, while in Part 2, it will be assessed at 60 minutes post-injection of a 200 MBq dose. Secondary endpoints will further explore **SUVmax** at 60 minutes post-injection on days 1 and 8, as well as other pharmacokinetic parameters such as Cmax, Tmax, AUC, Vd, clearance, and T1/2. Tumor visibility will also be evaluated using a numerical rating scale (NRS) ranging from 0 to 2, at specified time points and frame durations. These assessments aim to determine the diagnostic performance of uPAR PET imaging in classifying ISUP grades among patients with localized, untreated prostate cancer.