Clinical Trials

Inclusion Criteria:

- Capable of giving signed informed consent as described which includes compliance with
the requirements, restrictions listed in the informed consent form (ICF), and in this
protocol.

- Male ≥18 years of age at the time of signing the informed consent.

- Histologically or cytologically confirmed adenocarcinoma of prostate.

- Prostate cancer initially treated by: radical prostatectomy (RP) followed by adjuvant
radiotherapy (ART), or salvage radiotherapy (SRT), or RP in participants who are unfit
(or refused) for ART or SRT, or primary radiotherapy (RT).

- High-risk biochemical recurrence (BCR), defined as Prostate-specific antigen doubling
time (PSADT) <12 months calculated using the formula provided by the Sponsor, and PSA
≥0.2 ng/mL after ART or SRT post RP or after RP in participants who are unfit for ART
or SRT (local or central values accepted), or PSA ≥2 ng/mL above the nadir after
primary RT only (local or central values accepted).

- Participants must undergo prostate-specific membrane antigen positron emission
tomography/computed tomography (PSMA PET/CT) within the 42-day Screening period using
either 18F-DCFPyL (piflufolastat F 18) or 68Ga-PSMA-11 which will be assessed by
blinded independent central review (BICR) to identify at least one PSMA PET/CT lesion
of prostate cancer.

- Serum testosterone ≥150 ng/dL (5.2 nmol/L) (local or central values accepted).

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Blood counts at screening: Hemoglobin ≥9.0 g/dL (participant must not have received
blood transfusion within 7 days prior to sample being taken); Absolute neutrophil
count (ANC) ≥1.5x10^9/L (participant must not have received any growth factor within 4
weeks prior to sample being taken); Platelet count ≥100x10^9/L.

- Screening values of: Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal
(ULN); Aspartate aminotransferase (AST) ≤1.5 x ULN; Total bilirubin (TBL) ≤1.5 ULN,
(except participants with a diagnosis of Gilbert's disease); Estimated glomerular
filtration rate (eGFR) >40 ml/min/1.73 m^2 calculated by the CKD-EPI formula.

- Sexually active male participants must agree to use contraception as detailed in the
protocol during the Treatment period and for at least 1 week after the last dose of
study treatment, and refrain from donating sperm during this period.

Exclusion Criteria:

- Pathological finding consistent with small cell, ductal or ≥50 % component of
neuroendocrine carcinoma of the prostate.

- History of bilateral orchiectomy.

- Metastases or recurrent /new malignant lesions in prostate gland/bed seminal vesicles,
lymph nodes below the CIA bifurcation on conventional imaging (CI) as assessed by BICR
during screening.

- Brain metastasis on PSMA PET /CT by BICR at screening.

- High-risk BCR after primary radiotherapy with new loco-regional lesions on screening
PSMA PET/CT who are eligible for curative salvage prostatectomy.

Note: Participants treated with curative salvage prostatectomy after primary RT who meet
the PSA criteria (inclusion criteria 5) may be considered for the study.

- Prior treatment with second generation (e.g. enzalutamide, apalutamide) androgen
receptor inhibitors (ARIs) and CYP 17 inhibitors (e.g., abiraterone) within 18 months
prior to signing of the ICF.

- Prior treatments with PSMA-radiotherapeutics within 12 months prior to randomization.

- Prior radiotherapy (including image-guided radiotherapy) as primary, adjuvant or
salvage treatment completed within 8 weeks prior to signing of the ICF.

- Any prior malignancy (other than adequately treated basal cell or squamous cell skin
cancer, superficial bladder cancer, or any other cancer in situ currently in complete
remission) within 5 years.

- History of pelvic radiotherapy for other malignancy.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 3/01/2024. Questions regarding updates should be directed to the study team contact.