Overview
To determine the dose, safety, radiation dosimetry and efficacy of 177Lu-rhPSMA-10.1 in participants with PSMA-expressing metastatic castrate resistant prostate cancer.
Description
This is an interventional, non-randomised, open-label, integrated Phase 1 & 2 study to assess the safety, radiation dosing regimen and anti-tumour activity of Lutetium (177Lu) rhPSMA-10.1 (Tx IMP) in men with metastatic castrate-resistant prostate cancer (mCRPC). The study will consist of 2 parts: a Phase 1, with safety, dose-finding, and dosimetry components, and a Phase 2, with assessment of efficacy and safety utilising the dose selected from Phase 1. Both phases will include subjects with prostate-specific membrane antigen (PSMA)-positive mCRPC as detected using 18F-rhPSMA-7.3 diagnostic IMP.
Eligibility
Inclusion Criteria:
- Male subjects, 18 years of age or older with histologically confirmed adenocarcinoma of the prostate.
- Serum testosterone levels <50 ng/dL (1.73 nmol/L) after surgical or continued chemical castration.
- 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.
- Positive disease expression of PSMA as confirmed on PSMA PET/CT scan.
- 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).
- 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).
- Prior major surgery must be at least 12 weeks prior to study entry.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with a life expectancy ≥6 months.
- Adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline.
- Adequate contraception for patients and their partners.
- Cohorts:
- Phase 1 and Phase 2 post-chemotherapy mCRPC
- Phase 2 taxane-naïve mCRPC
Exclusion Criteria:
- Known hypersensitivity to the therapeutic or diagnostic IMP or any of its constituents.
- Presence of significant PSMA-negative disease on ceCT/MRI scan
- Diffuse marrow infiltration of disease ('superscan' appearance on full body 99mTc bone scan).
- Symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression.
- Known history of haematological malignancy.
- Known history of central nervous system (CNS) metastases.
- Histological findings consistent with neuroendocrine phenotype of prostate cancer.
- Known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment.
- Unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy.
- 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.
- Ongoing treatment with bisphosphonates for bone-targeted therapy.
- Severe urinary incontinence that would preclude safe disposal of radioactive urine.
- 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.
- Clinically significant abnormalities on a single 12 lead electrocardiogram (ECG) at screening.
- Previously received external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys.
- Previous treatment with any of the following: PSMA targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium 186, Rhenium-188, Radium-223, hemi-body irradiation.
- Subjects with bilateral hip replacements or any significant metallic implants or objects, that may affect image quality and/or dosimetry calculations.