A Phase 2 Study to Evaluate the Safety and Immunological Efficacy of Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Patients With HER2 Expressing Gastric Cancer (CORNERSTONE-003)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 7
- 主要终点
- Number of participants with treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0.
研究概览
简要总结
The purpose of this early proof-of-concept study to evaluate the safety and immunologic efficacy of AST-301 in gastric cancer patients with HER2 expression (including both HER2 low expression and overexpression) who have completed the standard adjuvant treatment (including those who discontinued the standard adjuvant treatment due to intolerance).
Participants will be randomized 1:1 to either Arm 1 (Q3W, 3 cycles), or Arm 2 (Q3W, 6 cycles) of the study.
Safety Monitoring Committee (SMC) will oversee safety of study at 25% (6 participants), 50% (12 participants), and 75% (18 participants) of participants receive at least 1 dose of AST-301 and survival follow up will be performed to determine disease-free survival (DFS).
详细描述
Participants will provide informed consent and will undergo Pre-Screening/Screening procedures before taking part in the study. Participants will be in Arm 1 and Arm 2 will be conducted in parallel. AST-301 will be administrated every 3 weeks for a total of 3 immunizations in Arm 1 and a total of 6 immunizations in Arm 2.
- Arm 1: 3 immunizations of AST-301 admixed with immunoadjuvant recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF) administered at 3-week intervals. (Total 300 μg of AST-301)
- Arm 2: 6 immunizations of AST-301 admixed with immunoadjuvant recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF) administered at 3-week intervals. (Total 600 μg of AST-301) Randomization will be stratified according to HER2 expression (HER2 low expression or HER2 overexpression).
For both Arm 1 and Arm 2 of the study there will be a Pre-screen period, followed by study periods: a Screening Period (Day -28 to Day -1), a Treatment Period (3 cycles/Arm 1 and 6 cycles/Arm 2), an end of treatment (EOT) visit and follow-up visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Underwent a curative surgery with standard lymph node dissection (confirmed with no residual tumor, R0 resection) and have completed standard adjuvant treatment
- •Has stages II or III according to the 8th edition of the American Joint Committee on Cancer (AJCC)
- •HER2 low expression and HER2 overexpression diagnosed according to the 2016 College of American Pathologists (CAP)/American Society for Clinical Pathology (ASCP)/American Society of Clinical Oncology (ASCO) guidelines
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Demonstrates adequate organ function.
排除标准
- •Has a history of hypersensitivity or other contraindications to rhuGM-CSF
- •Has a history of other malignancies ≤5 years prior to first administration of Investigational Product (IP) except for adequately treated non-melanoma skin cancer or epithelial carcinoma without evidence of disease.
- •Has received systemic immunosuppressants or were treated with systemic immunosuppressants ≤4 weeks prior to the first administration of Investigational Product (IP).
- •Has a history of autoimmune disease or inflammatory disease
- •Has active infection including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
- •Is pregnant or breastfeeding or expecting to conceive children
研究组 & 干预措施
Total 300 μg of AST-301
AST-301/rhuGM-CSF (3-week interval, 3 cycles in total)
干预措施: AST-301 (Drug)
Total 300 μg of AST-301
AST-301/rhuGM-CSF (3-week interval, 3 cycles in total)
干预措施: rhuGM-CSF (Drug)
Total 600 μg of AST-301
AST-301/rhuGM-CSF (3-week interval, 6 cycles in total)
干预措施: AST-301 (Drug)
Total 600 μg of AST-301
AST-301/rhuGM-CSF (3-week interval, 6 cycles in total)
干预措施: rhuGM-CSF (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0.
时间窗: up to 20 weeks
To assess the safety of AST-301 administered in gastric cancer patients.
Immunologic efficacy of AST-301 immunization
时间窗: 52 weeks
AST-301 specific interferon (IFN)-gamma enzyme-linked immune absorbent spot (ELISpot) assay
次要结局
- 1year Disease-Free Survival rate (DFS rate)(12 months)
- Compare immunogenicity of AST-301 between Arm 1 and Arm 2(52 weeks)
- Change in central memory T-cell populations between Arm 1 and Arm 2(52 weeks)
- Disease-Free Survival rate (DFS rate) at end of study (EOS)(Overall study period approximately 31 months)