Evaluation of Copper Cu 64 PSMA I&T PET/CT for Detection of Pelvic Lymph Node Metastasis in High-Risk Prostate Cancer Pre-Prostatectomy Patients

The primary objective of this Phase 3, multicenter, open-label study is to determine the **diagnostic performance** of copper Cu 64 PSMA I&T PET/CT in detecting the presence or absence of pelvic lymph node metastasis in patients with newly diagnosed unfavorable intermediate-risk, high-risk, or very high-risk **prostate cancer** who are scheduled to undergo radical prostatectomy with pelvic lymph node dissection. This is clinically relevant as accurate staging of prostate cancer is crucial for determining the appropriate surgical and therapeutic interventions, potentially improving patient outcomes.

Secondary objectives include:

• Assessing inter- and intra-reader agreement of copper Cu 64 PSMA I&T PET/CT interpretation on a per-patient basis, which is important for ensuring consistency and reliability in diagnostic imaging.
• Evaluating the safety of copper Cu 64 PSMA I&T injection, which is essential for confirming the safety profile of the diagnostic agent used in this study.

The clinical trial involves a total of **173 participants** diagnosed with **prostate cancer**. The study population consists exclusively of male subjects aged 18 years and older, with no female participants included. Participants are required to have histologically confirmed prostate adenocarcinoma and are scheduled for prostatectomy with pelvic lymph node dissection. The trial targets individuals with unfavorable intermediate-risk, high-risk, or very high-risk disease as defined by the NCCN Guidelines Version 1.2023. The selection process ensures that participants are capable of understanding and providing signed written informed consent. The trial does not include any vulnerable populations. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is a **Phase 3**, multicenter, open-label study designed to evaluate the diagnostic performance of **Copper Cu 64 PSMA I&T PET/CT** in staging men with newly diagnosed unfavorable intermediate-risk, high-risk, or very high-risk **prostate cancer** who are electing to undergo radical prostatectomy with pelvic lymph node dissection. The trial aims to determine the sensitivity and specificity of the imaging technique in detecting pelvic lymph node metastasis, using histopathology as the reference standard. The study is expected to commence recruitment on October 15, 2024, and conclude by June 30, 2025.

Participants will be involved in the study for a period that includes several key visits. Initially, an inclusion (screening) visit will be conducted to confirm eligibility based on criteria such as histologically proven prostate adenocarcinoma, planned prostatectomy with pelvic lymph node dissection, and specific risk categories as defined by NCCN Guidelines. Eligible participants must be male and aged 18 years or older, with the ability to provide informed consent. Following the screening, participants will undergo the investigational product administration, which involves a single **intravenous injection** of **64Cu-PSMA I&T**. The maximum daily and total dose is 8.8 mCi, with a treatment period limited to one day.

Subsequent study visits will include follow-up assessments to monitor for treatment-emergent adverse events, which will be recorded from the time of investigational product administration up to 72 hours post-administration. The end-of-study visit will mark the completion of the participant's involvement in the trial. The expected length of participant involvement is approximately one week, encompassing the screening, administration, and follow-up phases. Conditions that may lead to early termination from the study include withdrawal of consent or the occurrence of significant adverse events that compromise participant safety.

The clinical trial involves the use of the experimental medication **64Cu-PSMA I&T**, which is a **solution for injection**. This investigational product is administered via **intravenous injection**. The active substance, **64Cu-PSMA I&T**, is of chemical origin and is provided by Curium US LLC. The maximum daily dose and the maximum total dose for the treatment period is 8.8 mCi (millicurie(s)). The treatment period is limited to a single day. The medication is not formulated for pediatric use and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the diagnostic performance of the experimental medication. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial aims to assess the efficacy of **64Cu-PSMA I&T** in detecting pelvic lymph node metastasis in patients with newly diagnosed unfavorable intermediate-risk, high-risk, or very high-risk prostate cancer who are electing to undergo radical prostatectomy with pelvic lymph node dissection.

Efficacy in this clinical trial will be assessed by evaluating the diagnostic performance of **copper Cu 64 PSMA I&T PET/CT** in detecting pelvic lymph node metastasis in patients with newly diagnosed unfavorable intermediate-risk, high-risk, or very high-risk prostate cancer. The primary endpoints include the sensitivity and specificity of the PET/CT scan relative to a histopathology reference standard. Sensitivity will be determined by identifying at least one positive pelvic lymph node on the PET scan and a corresponding positive lymph node as determined by histopathology on the same side of the pelvis, which will be counted as a true positive at the patient level. Specificity will be assessed by identifying negative pelvic lymph nodes on both the PET scan and histopathology, counted as a true negative at the patient level.

Secondary endpoints include the reader kappa statistics for the interpretation of the PET/CT scans by blinded independent readers, as well as the monitoring of treatment-emergent adverse events from the time of investigational product administration up to 72 hours. The trial is designed as a Phase III, multicenter, open-label study, with the estimated recruitment start date set for October 15, 2024, and an estimated end date of June 30, 2025. The study will involve patients who are scheduled for prostatectomy with pelvic lymph node dissection, and who meet the inclusion criteria based on the NCCN Guidelines Version 1.2023 and previous versions.