A Phase II Study of AAA617 Alone and AAA617 in Combination With ARPI in Patients With PSMA PET Scan Positive CRPC

Key Inclusion criteria

- Participants must be adults ≥ 18 years of age with signed informed consent prior to
participation to study

- Histologically or cytologically confirmed prostate cancer

- Participants must have ongoing androgen deprivation therapy with a GnRH
agonist/antagonist or prior bilateral orchiectomy

- Castrate level of serum testosterone (< 1.7 nmol/l [50 ng/dl]) on GnRH agonist or
antagonist therapy or after bilateral orchiectomy

- Participants must have evidence of PSMA-positive disease as seen on a AAA517 or
piflufolastat F 18 PET/CT scan at baseline as determined by Blinded Independent
Central Review (BICR) based on the methodology proposed in the Prostate Cancer
Molecular Imaging Standardized Evaluation (PROMISE) (Eiber et al 2018). Participants
with M1 disease only on PSMA PET scan are allowed to participate

- Participants must have a negative conventional imaging for M1 disease.

- PSA Doubling Time (PSADT) of ≤ 10 months

- Participants must have adequate organ functions: bone marrow reserve, hepatic &
renal

Key Exclusion criteria

- Prior or present evidence of metastatic disease as assessed by CT/MRI locally for
soft tissue disease and whole-body radionuclide bone scan for bone disease.
Exception: Participants with soft tissue pelvic disease may be eligible (e.g.,
participants with enlarged lymph nodes below the aortic bifurcation (N1) are
eligible if the short axis of the largest lymph node is <20 mm)

- Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note:
participants with bladder outflow obstruction or urinary incontinence, which is
manageable with best available standard of care (incl. pads, drainage) are allowed

- Active clinically significant cardiac disease; history of seizure or condition that
may pre-dispose to seizure which may require treatment with surgery or radiation
therapy

- Prior therapy with: second generation anti-androgens (e.g., enzalutamide,
apalutamide and darolutamide); CYP17 inhibitors (e.g., abiraterone acetate,
orteronel, galeterone, ketoconazole; radiopharmaceutical agents (e.g.,
Strontium-89), PSMA-targeted radioligand therapy; immunotherapy (e.g.,
sipuleucel-T); chemotherapy, except if administered in the adjuvant/neoadjuvant
setting, completed > 2 years before randomization; any other investigational agents
for CRPC; use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride),
other steroidogenesis inhibitors (aminoglutethimide) or first-generation
anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone) within 28 days
before randomization; radiation therapy (external beam radiation therapy [EBRT] and
brachytherapy within 28 days before randomization

- Other concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, poly
adenosine diphosphate-ribose polymerase (PARP) inhibitor, biological therapy or
investigational therapy

Other protocol-defined inclusion/exclusion criteria may apply.