The goal of this clinical trial is to study a personalized regime of lutetium-177 (177Lu) prostate-specific membrane antigen (PSMA) radiopharmaceutical therapy (RPT) in patients with progressive and/or symptomatic, inoperable PSMA-expressing cancers of prostatic or other origins.

The main questions it aims to answer are:

• To establish a dosimetry-based, personalized regime of 177Lu-PSMA
• To report on the efficacy of personalized 177Lu-PSMA

Participants (stratified by risk factors of toxicity) will receive up to 6 cycles of a personalized activity of 177Lu-PSMA based on renal dosimetry. In the phase 1, the prescribed absorbed dose to the kidney will be escalated, to determine the regime that will be administered in the phase 2. The best response within 12 months after the first cycle will be assessed. Salvage treatment of 3 cycles may be offered to responders after re-progression.

Inclusion Criteria:

• >18 y.o. adults able to provide consent
• Inoperable or metastatic PSMA-expressing cancer, with significant PSMA expression defined as uptake in at least one lesion that is superior to that of the liver on PSMA positron-emission tomography (PET) within 3 months prior to enrolment
• Cancer progression documented within 3 months prior to enrolment as per the investigator's assessment, without initiation of another anti-cancer treatment since (excluding palliative radiation therapy to a minority of the tumor burden), unless that anti-cancer treatment was stopped prematurely because of intolerance
• For participants with a cancer other than mCRPC, a recommendation from a multidisciplinary tumor board (MDT) in favor of PSMA RPT must be obtained

Exclusion Criteria:

• Platelets < 50 x 106/L
• Absolute neutrophil count (ANC) < 1.0 x 106/L
• Eastern Cooperative Oncology Group (ECOG) 4 or prognosis < 3 months, for cancer-related or other serious medical conditions, as per investigator's assessment
• Known presence of central nervous system metastasis at risk of complication, which cannot be adequately stabilized (e.g. radiotherapy or corticoid prophylaxis), as per investigator's assessment
• Any condition that would limit the ability to comply with the study protocol, as per investigator's assessment
• Pregnancy or breastfeeding (e.g. for female participants with non-prostate cancer)