A Phase I, Single-Arm, Open-Label, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of Autologous Neoantigen-Pulsed Dendritic Cell Vaccine (YS247) in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 18
- 试验地点
- 1
研究概览
简要总结
This phase I study tests a personalized cancer vaccine (Neo-DC) for men with advanced prostate cancer (metastatic castration-resistant prostate cancer, or mCRPC) that has continued to grow despite standard hormone therapies and other treatments.
The vaccine is custom-made for each participant using their own immune cells (dendritic cells) mixed with specific tumor markers (neoantigens) unique to their cancer. These neoantigens are identified through genetic sequencing of the patient's tumor. The goal is to help the body's immune system recognize and attack the cancer cells specifically.
The study will enroll approximately 9 to 18 men and will test three different dose levels to find the safest amount. Participants will receive the vaccine as an injection under the skin every two weeks for a total of 4 doses over an 8-week treatment period.
The main purpose is to evaluate the safety of this vaccine, determine the maximum tolerated dose, and identify any serious side effects. Researchers will also look at whether the vaccine helps lower PSA levels (a blood marker for prostate cancer), slows cancer growth, and stimulates an immune response against the tumor.
Participants will be monitored closely during treatment and followed for several months afterward to assess long-term safety and effects.
详细描述
This is a phase I, single-center, open-label, dose-escalation study evaluating the safety, tolerability, and preliminary efficacy of an autologous neoantigen-pulsed dendritic cell vaccine (Neo-DC, also known as YS247) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Study Design:
The study employs a traditional "3+3" dose-escalation methodology with three sequential dose cohorts: 5×10⁶, 1×10⁷, and 1.5×10⁷ cells per injection. A sentinel dosing approach will be used within each cohort, where the first participant is observed for 4 weeks before subsequent participants are enrolled at that dose level.
Intervention:
The investigational product is an autologous cellular immunotherapy manufactured from patient-derived peripheral blood mononuclear cells (PBMCs) obtained via leukapheresis. Dendritic cells are differentiated ex vivo, loaded with personalized neoantigens identified through next-generation sequencing (NGS) of tumor tissue (fresh biopsy or archival specimen), and matured using cytokine activation (GM-CSF, IL-4, TNF-α, IFN-γ, PGE2). The final product is administered as a subcutaneous injection (0.3 mL per site, 1-3 sites per dose) in the axillary or inguinal regions every 2 weeks for 4 doses (total 8-week treatment period).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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).
- •Symptomatic central nervous system metastases.
- •Uncontrolled active or persistent infection requiring systemic therapy.
- •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.
- •Known, confirmed, or suspected autoimmune disease or immunosuppressive condition.
- •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.
- •Active autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus).
- •Receipt of live vaccines within 4 weeks prior to first study treatment or planned during the study period.
- •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.
- •High tumor burden as assessed by imaging, deemed unsuitable by the investigator.