Exploratory Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247) in Patients With Recurrent or Progressive Glioblastoma
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 9
- 主要终点
- Safety and Treatment Tolerability
研究概览
简要总结
This is a single-center, open-label, dose-escalation, multiple-dose investigator-initiated trial (IIT). The trial aims to evaluate the safety and tolerability of autologous dendritic cell injection sensitized with tumor neoantigens (YS247) in participants with recurrent or progressive glioblastoma, as well as to assess preliminary efficacy and pharmacodynamic characteristics. The study consists of four phases: screening, baseline, treatment, and follow-up. During the treatment phase, participants will be assigned to three dose groups (low, medium, and high) and enrolled following the "3+3" dose-escalation principle. YS247 will be administered subcutaneously once every 2 weeks for a total of 8 consecutive doses.
详细描述
A total of 9 to 18 participants are planned to be enrolled in this study. A dose-escalation design will be adopted following the 3+3 escalation principle, and the injection dose of the study drug YS247 is preset at three dose levels (low, medium, high) as specified below, with 3 to 6 participants planned to be enrolled in each dose level group. An adaptive trial design will be implemented, where the number of enrolled participants in each group will be adjusted based on the actual clinical study results
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years (inclusive), any gender.
- •Histologically confirmed GBM (WHO Grade IV).
- •Recurrence/progression confirmed by MRI after standard therapy (surgery, Stupp protocol); ≥1 measurable lesion (max diameter ≥1.0 cm) on contrast-enhanced MRI per RANO criteria.
- •KPS score ≥60, expected survival ≥6 months.
- •ECOG score 0-
- •Bridging therapy allowed during sample preparation; washout ≥7 days or 5 half-lives (whichever longer) before initial treatment.
- •Radiotherapy completed ≥8 weeks before study drug initiation.
- •Toxicity from prior anti-tumor therapy recovered to CTCAE V5.0 Grade 1 or below (except alopecia).
- •Adequate organ function:
- •ANC ≥1.5×10⁹/L, ALC ≥0.8×10⁹/L, HGB ≥90 g/L, PLT ≥100×10⁹/L
- •AST/ALT ≤2.5×ULN, TBIL ≤2.5×ULN, ALB ≥3 g/dL, ALP ≤2.5×ULN
- •INR/APTT ≤1.5×ULN (except therapeutic anticoagulation)
- •Cr ≤1.5×ULN or CrCl ≥60 mL/min (Cockcroft-Gault)
- •Normal ECG, LVEF ≥50% (ECHO)
- •Resting SpO₂ >92% without oxygen
- •Adequate venous access for PBMC collection, no contraindications.
- •Sufficient tumor and blood samples for NGS via resection or biopsy.
- •Negative serum pregnancy test (fertile females); effective contraception throughout screening, study, and 6 months after last dose for fertile participants/partners.
- •Compliance with study procedures and follow-up.
- •Voluntary participation and signed informed consent.
排除标准
- •Any other active malignancy.
- •Participation in another clinical trial within 4 weeks before enrollment.
- •Prior gene transfer therapy.
- •Concurrent anti-tumor therapy within 4 weeks before initial treatment (except allowed bridging); blood transfusion, EPO, G-CSF, or GM-CSF within 14 days before PBMC apheresis.
- •Live virus/recombinant vaccine within 4 weeks before first treatment; expected need for live attenuated vaccine within 6 months after last dose.
- •Severe allergy or hypersensitivity.
- •MRI contrast contraindications (pacemaker, pump, contrast allergy).
- •Positive HIV, HBV, HCV, or TP.
- •Primary/secondary immunodeficiency or autoimmune disease (SLE, RA, IBD, autoimmune thyroid disease, autoimmune hepatitis, MS, vasculitis, glomerulonephritis, psoriasis, uncontrolled asthma).
- •Severe infection within 1 month before treatment, uncontrolled infection, or antibiotics in the past week (except prophylaxis).
- •Systemic immunosuppressive therapy within 30 days before initial treatment (short-term use allowed with sponsor approval; permitted: inhaled steroids, mineralocorticoids, low-dose steroids ≤10 mg/day prednisone equivalent).
- •Uncontrolled systemic disease (NYHA III/IV heart failure, unstable angina, MI, cirrhosis, renal failure, severe lung disease, hematological/gastrointestinal/organ failure, diabetes, uncontrolled hypertension).
- •ICD-11 psychiatric/neurological disorders (epilepsy, schizophrenia, dementia, addiction) per investigator judgment.
- •Clinically significant bleeding within 3 months or bleeding diathesis; arterial/venous thromboembolism within 6 months (TIA, stroke, DVT, PE).
- •Irreversible electrolyte imbalance.
- •Anti-tumor therapy before apheresis: cytotoxic within 14 days; investigational within 28 days; immunomodulator within 7 days; targeted within 28 days.
- •Pregnant or lactating female.
- •Any other condition deemed unsuitable by the investigator.
结局指标
主要结局
Safety and Treatment Tolerability
时间窗: From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days)
Evaluate the incidence of treatment-related adverse events (TRAEs) of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247, Beijing YSCell Biotech Co., Ltd., abbreviated as YS) in patients with recurrent or progressive glioblastoma based on CTCAE v5.0, to assess the safety and tolerability of the product.
Maximum Tolerated Dose (MTD) and Recommended Expanded Dose(RP2D)
时间窗: From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days)
Based on the incidence of dose-limiting toxicities (DLTs), establish the MTD of Tumor Neoantigen-pulsed Autologous Dendritic Cell Injection (YS247) for patients with recurrent or progressive glioblastoma, and define the RP2D. DLT is defined as any study drug-related AE (per CTCAE 5.0) or laboratory abnormality occurring from first dose to 4 weeks post-dose, unrelated to disease progression, comorbidity, or concomitant medication, including: 1. CTCAE Grade 3 non-hematological toxicity lasting \>7 days. 2. Immune-related Grade 3 pneumonia, recurrent Grade 2 pneumonia. 3. Other Grade 3 irAE not recovering to ≤Grade 2 in 3 days or ≤Grade 1 in 14 days with intervention. 4. CTCAE Grade 4 non-hematological toxicity. 5. CTCAE Grade 4 hematological toxicity lasting \>7 days. 6. CTCAE Grade 5 toxicity of any type. 7. Any unexpected toxicity requiring treatment termination per investigator/sponsor judgment.
次要结局
- Disease Control Rate (DCR)(From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days))
- Duration of Response (DoR)(From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days))
- the safe and efficacious dose range(From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days))
- Objective Response Rate (ORR)(From subject enrollment until completion of the 8th treatment cycle (each cycle is 14 days))