Clinical Evaluation of SRT-017 in Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer

To Evaluate the Safety, Tolerability, Radiation Dosimetry, Pharmacokinetics, and Preliminary Antitumor Efficacy of SRT-017 in Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This is a single-arm, open-label study to evaluate the safety, tolerability and preliminary anti-tumor efficacy of SRT-017 radioligand therapy in patients with PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC). All eligible participants will receive SRT-017 intravenous treatment. The primary objectives are to assess safety and tolerability. Secondary objectives include radiation dosimetry, pharmacokinetics, and preliminary antitumor activity.

Inclusion Criteria:

• Male participants aged 18 years or older.
• Histologically or cytologically confirmed prostate adenocarcinoma with metastatic castration-resistant prostate cancer (mCRPC). mCRPC is defined as disease progression under continuous androgen-deprivation therapy (ADT) or after prior bilateral orchiectomy, with serum testosterone maintained at castrate level (<50 ng/dL or <1.7 nmol/L), meeting at least one of the Prostate Cancer Working Group 3 (PCWG3) progression criteria: PSA progression (PSA ≥1 ng/mL, ≥25 % increase compared with PSA nadir with an absolute rise ≥2 ng/mL confirmed by two consecutive measurements at least 1 week apart); or radiographic progression (≥2 new bone metastatic lesions on bone scan, or soft-tissue disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)).
• Disease progression after treatment with at least one novel androgen-axis drug (NAAD), including abiraterone, enzalutamide, apalutamide, or darolutamide.
• Prior chemotherapy, or participants who are ineligible for chemotherapy or decline chemotherapy.
• PSMA-positive lesions confirmed by PSMA-PET/CT imaging; PSMA-positive is defined as tumor lesion uptake higher than liver background uptake.
• At least one measurable lesion by RECIST 1.1 criteria OR at least one bone metastasis lesion by PCWG3 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1.
• Estimated life expectancy of at least 6 months.
• No transfusion of blood products, hematopoietic growth factors, or albumin within 14 days before baseline laboratory tests, and adequate organ function as follows: hematologic: absolute neutrophil count ≥ 1.5 × 10⁹/L, white blood cell count ≥ 3.0 × 10⁹/L, platelet count ≥ 100 × 10⁹/L, hemoglobin ≥ 9 g/dL; hepatic: albumin ≥ 30 g/L, total bilirubin ≤ 1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) / aspartate aminotransferase (AST) ≤ 3 × ULN (without liver metastases) or ALT/AST ≤ 5 × ULN (with liver metastases); renal: serum creatinine ≤ 1.5 × ULN; coagulation: international normalized ratio (INR) ≤ 1.5, activated partial thromboplastin time (APTT) ≤ 2 × ULN.
• Willing to comply with radiation-protection instructions and scheduled study follow-up procedures.
• Able to understand study procedures and voluntarily provide written informed consent, and willing to comply with all study-related assessments and follow-up requirements.

Exclusion Criteria:

• Participants unable to tolerate required imaging examinations.
• Received systemic anti-tumor therapy (chemotherapy, radiotherapy, immunotherapy; endocrine therapy is exempt), investigational medicinal products, or investigational medical devices within 4 weeks prior to first study drug administration.
• Received prior radiopharmaceutical therapy (such as strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, lutetium-177) within 6 months before first dose; or received external-beam radiation therapy (EBRT) within 2 months before first dose.
• Persistent Grade 4 myelosuppression from prior anti-cancer therapy within 2 weeks before screening, or Grade 3 myelosuppression with recovery duration longer than 6 weeks.
• Plan to receive cytotoxic chemotherapy, anti-tumor immunotherapy, radioligand therapy, or other similar anti-cancer treatments during study participation.
• Known brain metastases identified at screening.
• History of other malignant neoplasms within the past 5 years (curative-treated localized tumors such as basal-cell or squamous-cell skin cancer are permitted).
• Symptomatic or impending spinal cord compression.
• Prior external-beam radiation therapy covering more than 25 % of bone-marrow-containing skeletal regions.
• Significant uncontrolled cardiovascular disease at screening: QTcF > 470 ms or known long QT syndrome; myocardial infarction, angina pectoris, or coronary artery bypass graft (CABG) within 6 months before screening and judged unsuitable for study entry by investigator.
• Uncontrolled bladder-outlet obstruction, urinary incontinence, claustrophobia, or radiophobia at screening.
• Positive screening serology for hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, or syphilis antibody.
• Hepatitis B surface antigen (HBsAg) positive with active hepatitis B virus (HBV) replication as assessed by HBV-DNA testing and investigator judgment.
• Known hypersensitivity to proteins/peptides, drug excipients, or structurally related compounds.
• Documented history of drug or alcohol abuse or chronic substance dependence within 1 year prior to screening.
• Unwilling to practice effective contraception during study participation and for 6 months after last study drug administration.
• Severe active ongoing infection at the time of first planned study drug administration.
• Any other medical condition which, in the investigator's judgment, may compromise participant safety, interfere with study result interpretation, or confer unacceptable participant risk.