Phase Ib/IIa Dose Escalation and Expansion Study of [²¹²Pb]Pb-ADVC001 in Metastatic Prostate Cancer (TheraPb - Phase I/II Study).

Inclusion Criteria

• •Documented metastatic adenocarcinoma of the prostate, confirmed by histopathology.
• •Progressive metastatic prostate cancer demonstrated by at least one of the following:
• •1. Increase in PSA greater than 25% and \> 2 ng/mL above nadir, confirmed by progression at two timepoints at least three weeks apart
• •2. Progressive disease or new lesion(s) (relative to previous imaging) in the viscera or lymph nodes as per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or in bone as per Prostate Cancer Clinical Trials Working Group 3 (PCWG3).
• •For Phase 1b Dose Escalation: Metastatic castration-resistant prostate cancer (mCRPC) with exposure to at least one ARPi and taxane-based chemotherapy at any time in the course of their disease (unless taxanes considered contraindicated or declined by participant as documented in the patient's source documents and eCRF).
• •For Phase 2a Dose Expansion:
• •1. Group 1: Metastatic hormone-sensitive prostate cancer (mHSPC) with a sub-optimal PSA response defined as PSA ≥ 0.2 ng/mL despite receiving androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPi) without evidence of disease progression
• •2. Group 2: Progressive mCRPC post ≥ 1 ARPi; 177Lutetium (177Lu)-PSMA-naïve and not previously treated with chemotherapy for CRPC
• •3. Group 3: Progressive mCRPC with prior exposure to 177Lu-PSMA and ARPi
• •Has disease that is prostate specific membrane antigen (PSMA) positive, as demonstrated by ⁶⁸Ga-PSMA-PET/CT or ¹⁸F-based PSMA PET/CT and confirmed as eligible by local reader. PSMA-positive participants are defined as those having at least one tumor lesion with ⁶⁸Ga- or ¹⁸F- PSMA PET CT uptake greater than normal liver (based on visual assessment) and all tumor lesions larger than size criteria with ⁶⁸Ga- or ¹⁸F-PSMA uptake greater than liver \[short axis size criteria: organs ≥ 1 cm, lymph nodes ≥ 2.5 cm, bones (soft tissue component) ≥ 1 cm\].
• •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• •Adequate haematological, renal, and liver function.