Anti-tumour Activity of (177Lu) RhPSMA-10.1 Injection

Eligibility Criteria

• 1. Male subjects, 18 years of age or older with histologically confirmed adenocarcinoma of the prostate.
• 2. Serum testosterone levels \<50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration.
• 3. Presence of disease target or non target lesions (per RECIST v1.1) on CT/MRI and full body 99mTc bone scan performed within 28 days of screening.
• 4. Positive disease expression of PSMA as confirmed on PSMA PET/CT scan.
• 5. At least 4 weeks or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinising Hormone-releasing Hormone or GnRH).
• 6. Resolution of all previous treatment related toxicities to CTCAE version 5.0 grade of ≤1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed).
• 7. Prior major surgery must be at least 12 weeks prior to study entry.
• 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months.
• 9. Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline.
• 10. Adequate contraception for patients and their partners.
• 11. Cohorts:
• 1. Phase 1 and Phase 2 post-chemotherapy mCRPC
• 2. Phase 2 taxane-naïve mCRPC
• 1. Known hypersensitivity to the therapeutic or diagnostic IMP or any of its constituents.
• 2. Presence of significant PSMA-negative disease on ceCT/MRI scan
• 3. Diffuse marrow infiltration of disease ('superscan' appearance on full body 99mTc bone scan).
• 4. Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression.
• 5. Known history of haematological malignancy.
• 6. Known history of central nervous system (CNS) metastases.
• 7. Histological findings consistent with neuroendocrine phenotype of prostate cancer.
• 8. Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment.
• 9. Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy.
• 10. Any uncontrolled significant medical, psychiatric, or surgical condition or laboratory finding that would pose a risk to subject safety or interfere with study participation or interpretation of individual subject results.
• 11. Ongoing treatment with bisphosphonates for bone-targeted therapy.
• 12. Severe urinary incontinence that would preclude safe disposal of radioactive urine.
• 13. Single kidney or renal transplant or any concomitant nephrotoxic therapy that might put the subject at high risk of renal toxicity during the study in the judgement of the investigator.
• 14. Clinically significant abnormalities on a single 12 lead electrocardiogram (ECG) at screening.
• 15. Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys.
• 16. Previous treatment with any of the following: PSMA targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium 186, Rhenium-188, Radium-223, hemi-body irradiation.
• 17. Subjects with bilateral hip replacements or any significant metallic implants or objects, that may affect image quality and/or dosimetry calculations.