YS247 (Neoantigen-Pulsed DC Vaccine) for Metastatic Prostate Cancer

Prior treatment

• Systemic corticosteroid therapy within 4 weeks prior to enrollment (equivalent to \>20 mg/day prednisone).
• Prior immunomodulatory therapy within 3 months, including but not limited to IL-2, CTLA-4 inhibitors, PD-1/PD-L1 inhibitors, CD40 agonists, or CD137 agonists (except adjuvant IFN-α for high-risk melanoma).
• Prior investigational prostate cancer-targeted vaccine therapy or cellular therapy within 3 months.
• Receipt of other investigational products within 2 months prior to enrollment.
• History of severe allergic reaction to any prior vaccination (for infectious disease prevention).
• Major cardiovascular events within 6 months prior to first dose, including acute coronary syndrome, aortic dissection, or stroke; or presence of severe cardiovascular disease requiring clinical intervention.
• Receipt of live vaccines within 4 weeks prior to first study treatment or planned during the study period.

Other illness

• Uncontrolled active or persistent infection requiring systemic therapy.
• Known, confirmed, or suspected autoimmune disease or immunosuppressive condition.
• Active autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus).
• Uncontrolled hypertension (despite optimal medical management).
• Substance abuse or any psychological condition that, in the investigator's judgment, may interfere with study participation or results.
• Investigator's assessment of insufficient compliance or presence of other severe systemic diseases that would make the participant unsuitable for the study.

Age

• History of other malignancies within the past 5 years (except non-melanoma skin cancer or carcinoma in situ with documented disease-free survival \>5 years).

Other

• Symptomatic central nervous system metastases.
• High tumor burden as assessed by imaging, deemed unsuitable by the investigator.

• Male, age ≥18 years, with life expectancy ≥6 months.
• Histologically confirmed prostate adenocarcinoma with documented metastatic disease (bone, lymph nodes, or visceral organs) by recent whole-body MRI, bone scintigraphy (ECT), or PSMA-PET/CT.
• Confirmed metastatic castration-resistant prostate cancer (mCRPC) with documented disease progression after ≥1 line of novel endocrine therapy (e.g., abiraterone or enzalutamide).
• ECOG performance status 0-1.
• Availability of tumor tissue (fresh biopsy or archival specimen) for neoantigen screening.
• Willingness to undergo long-term follow-up.
• Provision of signed informed consent form by participant or legally authorized representative prior to study procedures.
• Willingness to undergo prostate biopsy if required for tissue acquisition. Adequate organ function as defined by laboratory values at screening: Absolute neutrophil count (ANC) \>1.5×10⁹/L; Platelet count \>100×10⁹/L; Hemoglobin \>90 g/L; Total bilirubin, ALT, and AST within normal laboratory limits; Serum creatinine \<133 μmol/L (or \<1.5 mg/dL); INR \<1.3 (or \<3.0 if on warfarin or other anticoagulants); Albumin \>30 g/L; Left ventricular ejection fraction (LVEF) ≥45% Negative for HIV, HBV (HBV DNA ≤500 IU/mL acceptable), and HCV (HCV RNA negative); No clinically significant ECG abnormalities.