177Lu-HTK03170 in mCRPC With PSMA Positive Disease

Prior treatment

• Prior treatment with 225Ac-PSMA-617, 177Lu-PSMA, other radiolabeled therapeutic PSMA-ligands, or radio-immunotherapy
• Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or targeted therapy) within 28 days prior to day of enrollment
• Radiotherapy to target lesions (measurable disease) ≤ 4 weeks prior to enrolment
• Other concomitant active invasive cancer (except superficial non-melanomatous, non-metastatic skin cancer or non-invasive superficial transitional cell carcinoma \[TCC\])
• Clinically significant cardiac disease including:
  • History of unstable angina pectoris, symptomatic pericarditis, or myocardial infarction within 6 months prior to study entry.
  • History of documented congestive heart failure (New York Heart Association \[NYHA\] functional classification III-IV) or cardiomyopathy.
• Major surgery within 4 weeks of starting study treatment.

Other illness

• Active epidural disease (treated epidural disease is permitted)
• History of risk factors for xerostomia (ie, head and neck radiation, Sjögren's disease) or pre-existing xerostomia Grade ≥1

Other

• Subjects meeting any of the following exclusion criteria are not to be enrolled in the study.
• Known parenchymal brain metastases
• Unmanageable urinary tract obstruction or hydronephrosis

• Each subject must meet all of the following inclusion criteria to be enrolled in the study:
• Male subjects ≥ 18 years of age
• Willing and able to provide consent
• Life expectancy of \> 6 months
• Progression on treatment with abiraterone and/or enzalutamide, or similar next generation ARAT therapy, as determined by the investigator. Subjects who have received docetaxel in the castration-resistant setting are also eligible to participate. Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor is permitted.
• Pathologically confirmed prostate adenocarcinoma
• Subjects must have evidence of biochemical or imaging progression. Progression is defined as any one of the following:
  • Prostate-specific antigen progression: two consecutive rising PSA values from a baseline measurement with an interval of ≥ 1 week between measurements. Minimum PSA at screening visit is ≥ 2.0 µg/L.
  • Soft tissue disease progression on chest, abdomen, pelvis CT or magnetic resonance imaging (MRI; RECIST v1.1)
  • Bone progression: ≥ 2 new lesions on bone scan
• Eastern Cooperative Oncology Group (ECOG) performance score ≤2
• Prior orchiectomy, or if on luteinizing hormone releasing hormone (LHRH) agonist/antagonist, then testosterone \< 1.7 nmol/L or \< 50 ng/dL
• Adequate organ function:
  • Marrow i) Absolute neutrophil count ≥ 1.5 × 109 /L ii) Platelet count ≥ 100 ×109 /L iii) Hemoglobin ≥ 90 g/L with no transfusions in the past 2 weeks b) Kidney i) Estimated creatinine clearance ≥40 ml/min according to Cockroft-Gault equation: ((140 - age) × (weight in kg)) / (72 × (serum creatinine)) c) Liver: i) Bilirubin \< 1.0 × upper limit of normal (ULN) (or if bilirubin is between 1.5 to 2 × ULN, must have a normal conjugated bilirubin) ii) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN in the absence of liver metastases, and) ≤ 5.0 × ULN in the presence of liver metastases.
• Recovery from all previous cancer treatment toxicities to grade ≤ 2 (as per CTCAE 4.03)
• Able to comply with scheduled visits, treatment plans, laboratory tests, imaging tests, and other procedures required and detailed in the protocol.
• Must be surgically sterile or use adequate contraception for the duration of the therapy and 6 months after the end of therapy