Exploring Auger-Enhanced PSMA-Targeted Radioligand Therapy: A First-in-Taiwan Clinical Study of 161Tb-PSMA-I&T

Prior treatment

• Prior radioligand therapy with 223Ra or 177Lu-PSMA within 6 months
• Prior surgery or radiotherapy within 4 weeks prior to first investigational dose
• Prior systemic therapies against prostate cancer within 4 weeks, including androgen receptor pathway inhibitor, chemotherapy, targeted therapy such as PARP inhibitors (PARPi)
• Concurrent severe uncontrolled illness that may jeopardize patient safety, including uncontrolled infections

Other illness

• History of allergic reaction to PSMA-targeted compounds or radiometals
• Discordant disease on PET images: FDG-positive disease with minimal PSMA expression
• Known symptomatic brain metastases or leptomeningeal disease, symptomatic or impending cord compression unless appropriately treated beforehand
• Other active malignancy requiring systemic treatment
• Significant cardiovascular disease (e.g., recent myocardial infarction, unstable angina)

Other

• Urinary tract obstruction causing hydronephrosis unless appropriately treated beforehand

• Age ≥ 20 years, ability to understand and willingness to sign informed consent, cooperate with all study-related procedures and assessments including blood tests and imaging
• Histologically confirmed adenocarcinoma of the prostate with evidence of metastatic castration-resistant prostate cancer (mCRPC)
• Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone analog, with a serum testosterone level \<50 ng/dL (castrate range)
• Prior treated with at least one line of taxane-based chemotherapy unless medically unsuitable, and at least one line of androgen receptor pathway inhibitor (e.g., abiraterone, enzalutamide, apalutamide, or darolutamide)
• Prior treated with 177Lu-labeled PSMA RLT unless medically unsuitable or declined by the patient
• Progressive disease defined according to Prostate Cancer Clinical Trials Working Group 3: Either a PSA progression of more than 2 rising PSA values from baseline with intervals ≥ 1 week, or a soft-tissue progression on images per RECIST 1.1 criteria, or a bone progression on images with more than 2 new lesions
• Evidence of significant PSMA-avid lesions on 68Ga- or 18F-labeled PSMA PET/CT within 12 weeks prior to screening, which defined as 68Ga-PSMA or 18F-PSMA uptake greater than that of liver or spleen parenchyma (depend on the tracer used) in at least one metastatic lesion of any size in any organ system
• A life expectancy of ≥ 6 months and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate bone marrow and organ functions 9.1 Hemoglobin ≥ 10 g/dL without RBC transfusion within 4 weeks 9.2 Absolute neutrophil count ≥ 1.5 × 109/L 9.3 Platelet count ≥ 150 × 109/L 9.4 Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault) 9.5 AST and ALT ≤ 3 × ULN, total bilirubin ≤ 1.5 × ULN
• Willingness to comply with the use of medically acceptable forms of barrier contraception if sexually active