Evaluation of Copper Cu 64 PSMA I&T PET/CT for Detecting 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 pre-prostatectomy patients with unfavorable intermediate-risk, high-risk, or very high-risk **prostate cancer**. 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:

• To assess 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.
• To assess the safety of copper Cu 64 PSMA I&T injection, which is essential for evaluating the risk-benefit profile of the diagnostic agent.

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. Participants were selected based on their diagnosis of histologically proven prostate adenocarcinoma and are scheduled for prostatectomy with pelvic lymph node dissection. The trial specifically targets individuals with unfavorable intermediate-risk, high-risk, or very high-risk disease as defined by the NCCN Guidelines Version 1.2023 and previous versions. The participants are required to be capable of understanding and providing signed written informed consent. The study does not include female subjects or vulnerable populations. No specific lifestyle considerations such as diet or physical activity are mentioned for this trial.

The clinical trial is a **Phase III**, 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 modality in detecting pelvic lymph node metastasis relative to a histopathology 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. The initial visit, known as the inclusion or screening visit, will 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, aged 18 years or older, and capable of providing informed consent. Following the screening, participants will undergo the investigational procedure involving the administration of **64Cu-PSMA I&T** via intravenous injection, with a maximum daily dose of 8.8 mCi.

Subsequent follow-up visits will monitor the participants for treatment-emergent adverse events up to 72 hours post-administration. The primary endpoints will assess the presence or absence of metastatic pelvic lymph nodes, while secondary endpoints will include reader kappa statistics for scan interpretation by blinded independent readers. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any adverse events are addressed. Participants may be terminated early from the study if they experience significant adverse events or if they withdraw consent. The study is not classified as low intervention, and the investigational product is not a pediatric formulation or an orphan drug.

The clinical trial involves the use of **64Cu-PSMA I&T**, an experimental medication designed for diagnostic purposes in the staging of prostate cancer. The pharmaceutical form of **64Cu-PSMA I&T** is a **solution for injection**, and it is administered via **intravenous injection**. The maximum daily dose and total dose amount for this trial is 8.8 mCi (millicurie(s)), with a maximum treatment period of one day. The active substance, **64Cu-PSMA I&T**, is of chemical origin and is provided by Curium US LLC. This investigational product 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 the diagnostic performance 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. Compliance with the dosing schedule is monitored to ensure accurate assessment of the investigational product's diagnostic capabilities.

The efficacy of the 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 **copper Cu 64 PSMA I&T PET/CT** in determining the presence or absence of metastatic pelvic lymph nodes, respectively, relative to a histopathology reference standard. A true positive result is defined as at least one positive pelvic lymph node on the PET scan and one positive lymph node as determined by histopathology on the same side of the pelvis. Conversely, a true negative result is defined as a negative pelvic lymph node on the PET scan and negative pelvic lymph nodes as determined by histopathology on the same side of the pelvis.

Secondary endpoints include the reader kappa statistics of the **copper Cu 64 PSMA I&T PET/CT** scan interpretation by blinded independent readers and the assessment of treatment-emergent adverse events from the time of investigational product administration up to 72 hours. The efficacy parameters will be collected and analyzed using these predefined endpoints to ensure a comprehensive evaluation of the diagnostic performance of the investigational product in the specified patient population.