Dose Escalation and Efficacy Study of 212Pb-ADVC001 in Patients With Metastatic Castration Resistant Prostate Cancer.

This is a first-in-human, dose escalation and efficacy study of [212Pb]Pb-ADVC001 in participants with PSMA-positive metastatic Castration Resistant Prostate Cancer (mCRPC) who have not had prior exposure to [177Lu]Lu-PSMA based radioligand therapies.

Inclusion Criteria:Male and 18 years of age or older at the time of signing the consent form with metastatic adenocarcinoma of the prostate, defined by documented histopathology of prostate adenocarcinoma or metastatic disease typical of prostate cancer (i.e., Involving bone and /or lymph nodes)Patients with castration-resistant prostate cancer that have progressed on androgen receptor therapy and exposure to a taxane-based chemotherapy at any time in the course of their disease, unless considered contraindicated by a medical oncologist or patient declines treatmentProgressive disease with rising PSA level, defined by PCWG3 criteria (sequence of two rising values above a baseline at a minimum of 1-week intervals), and PSA > 20 ng/mL Significant PSMA avidity on [68Ga]Ga-PSMA PET/CT, defined as a minimum uptake of SUVmax of 20 at a site of disease, and SUVmax > 10 at sites of measurable disease ≥10 mm (unless subject to factors explaining a lower uptake, e.g., respiratory motion, reconstruction artefact) ECOG Performance status 0 to 2Adequate renal, bone and liver function (Absolute neutrophil count: ≥2 x 10^9/L , Hemoglobin: ≥90 g/L, Platelet count: >150,000 x 10^9/L, Serum creatinine: <1.5 x upper limit of normal (ULN) i.e ≤ 125 umol/L or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault formula, Serum total bilirubin: <1.5 x ULN (unless the patient has Gilbert's syndrome in which case direct bilirubin must be normal), Serum AST and ALT: <1.5 x ULN in the absence of liver metastases; <3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria)Estimated life expectancy >12 weeksWilling and able to comply with all study requirements, including the timing and nature of all required assessments (i.e., blood testing and scanning.)Have provided written Informed Consent for participation in this trial and can commence study treatment within 14 days after the completion of screeningExclusion Criteria:Prostate cancer with known significant sarcomatoid or spindle cell or neuroendocrine small cell componentsSite(s) of disease that are FDG positive with minimal PSMA expression defined as FDG intensity > 68Ga-PSMA activity or 68Ga-PSMA SUVmax < 10Sjogren's syndromeECOG status >2Prior treatment with [177Lu]Lu- or [225Ac]Ac-PSMA based radioligand therapyComplete or partial obstruction of outflow of a kidneyContraindications to the use of corticosteroid treatmentActive malignancy other than prostate cancer (excluding non-melanomatous skin cancers)Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safetySerious psychological, familial, sociological, or geographical condition that might hamper compliance with the study protocol and follow-up schedulePatients who are sexually active and not willing/able to use medically acceptable forms of barrier contraceptionSevere claustrophobia that may impact the participants ability to comply with all aspects of the imaging protocol