A study to test a new drug (TRP-001) given before prostate cancer surgery in patients with very high-risk Prostate cancer.”

Prior treatment

• Have received any prior treatment for prostate cancer (including hormonal, radiation/radioligand therapy, chemotherapy, immunotherapy or investigational treatments).
• Use of any investigational drug or requirement to use or continue using any prohibited concomitant medication within 28 days prior to trial treatment start.
• History of clinically significant cardiovascular disease including, but not limited to severe/unstable angina, myocardial infarction, clinically significant cardiac arrhythmia, having a cardiac pacemaker or prosthetic valve or coronary artery bypass within the last 3 years prior to trial treatment start, symptomatic congestive heart failure New York Heart Association (NYHA) Class 3 or 4, non-optimally treated uncontrolled hypertension BP > 150/100 mmHg in more than one visit during the last month prior to study entry.
• Significant medical conditions/concurrent illnesses that could jeopardize compliance with the protocol including, though not strictly limited to: a. Known history or ongoing myelodysplastic syndrome (MDS), AML or CML b. History of Sjogren disease or any other autoimmune disease requiring active immune suppressive treatment c. Major surgery within 4 weeks prior to study inclusion d. Uncontrolled or severe infection e. History of Head and Neck SCC treated with definitive RT f. History of prior autologous or allogeneic stem-cell transplantation or CAR-T cell treatment g. Known active alcohol or drug abuse h. Known hypersensitivity reaction to any of the components of study treatment

Other illness

• Any serious underlying medical condition that per investigator assessment could impair the ability of the patient to receive treatment or undergo the procedures outlined in the protocol with reasonable safety including the planned RPE + ePLND.
• Known active hepatitis B virus (HBV), active hepatitis C virus (HCV) or active human immunodeficiency virus (HIV) infection.
• Any other invasive malignancy within the last 2 years except for adequately treated basal or squamous cell carcinoma, curatively treated localized non-melanoma skin cancer or non-muscle invasive bladder cancer.

Other

• Significant urinary bladder voiding dysfunction that could impede efficient excretion of radioactive urine after treatment.

• Histologically confirmed diagnosis of prostate adenocarcinoma, with no neuroendocrine differentiation or small-cell or transitional-cell characteristics.
• Age ≥ 18 years
• Informed consent form (ICF) signed indicating that the patient understands the purpose of the study and the procedures required and is willing and able to participate in the study
• Sexually active patients must be willing to use condoms and other effective forms of contraception for the entire study participation, including at least three months from last treatment administration.
• Very high-risk patients who meet The National Comprehensive Cancer Network (NCCN) - guidelines criteria
• PSMA-avidity on [68Ga]Ga-PSMA-11 PET/CT of the primary tumour defined as focal uptake visually at least two times higher than background activity in accordance with the PRIMARY score 3-5 (Emmett, 2022)
• No evidence of distant metastasis (M0 staging) as determined by [68Ga]Ga-PSMA-11 PET/CT within 28 days before starting treatment.
• Eligible for and planned to undergo potentially curative radical prostatectomy (removal of the entire prostate and seminal vesicle plus extended pelvic lymph node dissection) (as determined by the investigator).
• Tumour tissue of both prostate biopsy and radical prostatectomy specimens is/ will be available for local histology review and reference pathology assessments.
• Treatment-naïve patient
• Adequate organ function (no blood transfusion or treatment with hematopoietic growth factors within 4 weeks prior to haematology screening)
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1.