Safety and Preliminary Diagnostic Performance of [⁶⁴Cu]Cu-RAX301 in Prostate Cancer

Inclusion Criteria:

Phase I

Participants must meet all of the following criteria to be eligible for enrollment:

1. Able to provide written informed consent prior to initiation of any study-specific procedures.
2. Male participants aged ≥18 years.
3. Histologically confirmed prostate cancer.
4. ECOG performance status 0 to 2.
5. Life expectancy of at least 6 months.
6. Clinically assessed as scheduled to undergo radical prostatectomy and pelvic lymph node dissection (including patients with localized disease, regional lymph node metastases, or oligometastatic prostate cancer), with no contraindications to surgery.
7. Participants must meet one of the following risk categories: unfavorable intermediate-risk, high-risk, or very high-risk prostate cancer, as defined according to the NCCN Guidelines (Version 2026, Version 5; PROS-2):

   1. Unfavorable intermediate-risk prostate cancer, defined as meeting any of the following criteria:

      * ISUP Grade Group (GG) 3; or
      * GG 2 with ≥50% of biopsy cores positive for prostate cancer; and/or
      * Presence of ≥2 intermediate-risk factors, including clinical stage cT2b or cT2c and PSA 10-20 ng/mL.
   2. High-risk prostate cancer, defined as meeting at least one high-risk feature but not meeting criteria for very high-risk disease, including:

      * Clinical stage cT3a; or
      * GG 4 or 5; or
      * PSA \>20 ng/mL.
   3. Very high-risk prostate cancer, defined as meeting at least two of the following criteria:

      * Clinical stage cT3b-cT4;
      * GG 4 or 5;
      * PSA \>40 ng/mL.
8. Creatinine clearance ≥50 mL/min, as calculated using the Cockcroft-Gault formula.
9. Male participants must agree to use highly effective contraception for 4 weeks after administration of the investigational product and must refrain from donating sperm during this period.

Phase II

Participants must meet all of the following criteria to be eligible for enrollment:

1. Able to provide written informed consent prior to initiation of any study-specific procedures.
2. Male participants aged ≥18 years.
3. Histologically confirmed prostate cancer.
4. ECOG performance status of 0-2.
5. Estimated life expectancy ≥6 months.
6. Creatinine clearance ≥50 mL/min, as calculated using the Cockcroft-Gault formula.
7. Male participants must agree to use highly effective contraception for 4 weeks after administration of the investigational product and must refrain from donating sperm during this period.

   Additional Inclusion Criteria Applicable to Cohort 1 (BCR Cohort) Only
8. Any clinically significant adverse events that occurred during prior therapies (e.g., chemotherapy, radiotherapy, immunotherapy) have resolved to CTCAE Grade ≤2 (with the exception of alopecia).
9. Participants have previously undergone definitive therapy.
10. Participants with suspected prostate cancer recurrence based on rising PSA levels following definitive therapy, defined as follows:

    1. Post-radical prostatectomy: detectable or persistently rising PSA levels, with PSA ≥0.2 ng/mL, confirmed by a second measurement showing PSA ≥0.2 ng/mL (per American Urological Association \[AUA\] recommendations); or
    2. Post-radiotherapy, cryotherapy, or brachytherapy: PSA increase of ≥2 ng/mL above the nadir, in accordance with the American Society for Radiation Oncology (ASTRO)-Phoenix consensus definition.

    Additional Inclusion Criteria Applicable to Cohort 2 (pre-RP Cohort) Only
11. Clinically assessed as scheduled to undergo radical prostatectomy and pelvic lymph node dissection (including patients with localized disease, regional lymph node metastases, or oligometastatic prostate cancer), with no contraindications to surgery.
12. Participants must meet one of the following risk categories: unfavorable intermediate-risk, high-risk, or very high-risk prostate cancer, as defined according to the NCCN Guidelines (Version 2026, Version 5; PROS-2):

    1. Unfavorable intermediate-risk prostate cancer, defined as meeting any of the following criteria:

       * ISUP Grade Group (GG) 3; or
       * GG 2 with ≥50% of biopsy cores positive for prostate cancer; and/or
       * Presence of ≥2 intermediate-risk factors, including clinical stage cT2b or cT2c and PSA 10-20 ng/mL.
    2. High-risk prostate cancer, defined as meeting at least one high-risk feature but not meeting criteria for very high-risk disease, including:

       * Clinical stage cT3a; or
       * GG 4 or 5; or
       * PSA \>20 ng/mL.
    3. Very high-risk prostate cancer, defined as meeting at least two of the following criteria:

       * Clinical stage cT3b-cT4;
       * GG 4 or 5;
       * PSA \>40 ng/mL.

Exclusion Criteria:

Phase I

Participants meeting any of the following criteria will be excluded from the study:

1. Known or suspected hypersensitivity to the active component(s) of \[⁶⁴Cu\]Cu-RAX301 Injection or any of its excipients.
2. Inability to complete \[⁶⁴Cu\]Cu-RAX301 Injection PET/CT imaging as required by the protocol.
3. Participation in another interventional clinical trial prior to signing the informed consent form, within 5 half-lives of the investigational product, or current participation in another interventional clinical trial; or prior participation in a radiopharmaceutical clinical trial with a washout period of less than 3 months prior to signing informed consent.
4. Receipt of any intravenous iodinated contrast agent within 24 hours prior to administration of the investigational product, or receipt of any high-density oral contrast agent (e.g., barium sulfate) within 5 days prior to dosing. Oral water-soluble contrast agents (e.g., compound diatrizoate meglumine oral solution) are permitted.
5. Prior treatment with androgen deprivation therapy (ADT) or any other neoadjuvant therapy.
6. Receipt of high-energy gamma radiation (\>300 keV) prior to dosing, within 5 half-lives of the investigational product.
7. QTcF interval ≥470 msec on 12-lead ECG (corrected using Fridericia's formula).
8. Any medical condition that, in the investigator's judgment, may compromise participant safety, protocol compliance, or interpretation of study results.

Phase II

1. Known or suspected hypersensitivity to the active component(s) of \[⁶⁴Cu\]Cu-RAX301 Injection or any of its excipients.
2. Inability to complete \[⁶⁴Cu\]Cu-RAX301 Injection PET/CT imaging as required by the protocol.
3. Participation in another interventional clinical trial prior to signing informed consent, within 5 half-lives of the investigational product, or current participation in another interventional clinical trial; or prior participation in a radiopharmaceutical clinical trial with a washout period of less than 3 months prior to signing informed consent.
4. Receipt of any intravenous iodinated contrast agent within 24 hours prior to administration of the investigational product, or receipt of any high-density oral contrast agent (e.g., barium sulfate) within 5 days prior to dosing. Oral water-soluble contrast agents (e.g., compound diatrizoate meglumine oral solution) are permitted.
5. Receipt of high-energy gamma radiation (\>300 keV) prior to dosing, within 5 half-lives of the investigational product.
6. QTcF interval ≥470 msec on 12-lead ECG (corrected using Fridericia's formula).
7. Any medical condition that, in the investigator's judgment, may compromise participant safety, protocol compliance, or interpretation of study results.

   Additional Exclusion Criteria Applicable to Cohort 1 (BCR Cohort) Only
8. Receipt of systemic anticancer therapy for prostate cancer within 90 days prior to dosing (including but not limited to androgen deprivation therapy, antiandrogens, gonadotropin-releasing hormone agonists or antagonists, bone-targeted radiopharmaceuticals, or radiotherapy).

   Exclusion Criteria - Applicable to Phase II Cohort 2 (pre-RP Cohort) Only
9. Prior treatment with androgen deprivation therapy (ADT) or any other neoadjuvant therapy.