A Phase 1 Multicenter Study Evaluating the Safety and Efficacy of ACE2016, an Allogeneic Anti-EGFR Conjugated Gamma Delta T Cell (gdT) Therapy in Adult Subjects With Locally Advanced or Metastatic Solid Tumors Expressing Epidermal Growth Factor Receptor (EGFR)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 9
- 主要终点
- Incidence of DLTs, AESIs, Grade 3 or higher TEAEs, TEAEs considered related to ACE2016, TEAEs resulting in death, SAEs, related SAEs, and TEAEs leading to treatment discontinuation will be summarized by cohort
研究概览
简要总结
ACE2016 is an off-the-shelf, allogeneic gamma delta T (gdT) cell therapy derived from healthy donors, that is under investigation for the treatment of Locally Advanced or Metastatic Solid Tumors Expressing Epidermal Growth Factor Receptor (EGFR).
The ACE2016-001 study is an open-label, Phase I, first-in-human (FIH) study that aims to evaluate the safety and tolerability, persistency, pharmacodynamics and efficacy of ACE2016 in patients with Locally Advanced or Metastatic Solid Tumors Expressing Epidermal Growth Factor Receptor (EGFR).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Locally advanced unresectable or metastatic solid tumors that have failed at least two lines of therapy (one of which must be targeted therapy)
- •At least one measurable lesion as defined by RECIST v1.1 criteria
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- •Adequate hematologic and renal, hepatic and cardiac function
- •Oxygen saturation via pulse oximeter ≥92% at rest on room air
排除标准
- •Prior treatment with a genetically modified cell therapy product targeting EGFR
- •History of allogeneic transplantation
- •Subjects with active CNS metastases
- •History or presence of clinically relevant Central Nervous System (CNS) disorder (e.g. epilepsy)
- •Clinically significant active infection
- •Human Immunodeficiency Virus (HIV) infection, active hepatitis B infection, or hepatitis C infection.
- •History of malignancies with the exception of certain treated malignancies with no evidence of disease.
- •Primary immunodeficiency disorder
- •Pregnant or lactating female
- •Any medical, psychological, familial, or sociological conditions that, in the opinion of the Investigator or Sponsor Medical Monitor, would impair the ability of the subject to receive study treatment or comply with study requirements, including understanding and rendering of informed consent
研究组 & 干预措施
ACE2016 AND PEMBROLIZUMAB: 3 DOSES
ACE2016 recommended dose, in combination with pembrolizumab. Lymphodepleting regimen followed by recommended dose of ACE2016, giving in combination with pembrolizumab.
干预措施: Pembrolizumab (Drug)
ACE2016 ONLY: 1 DOSE
ACE2016 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE2016.
干预措施: Cyclophosphamide (Drug)
ACE2016 ONLY: 1 DOSE
ACE2016 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE2016.
干预措施: Fludarabine (Drug)
ACE2016 ONLY: 1 DOSE
ACE2016 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE2016.
干预措施: ACE2016 (Drug)
ACE2016 ONLY: 3 DOSES
ACE2016 recommended dose, monotherapy. Lymphodepleting regimen followed by recommended dose of ACE2016.
干预措施: Cyclophosphamide (Drug)
ACE2016 ONLY: 3 DOSES
ACE2016 recommended dose, monotherapy. Lymphodepleting regimen followed by recommended dose of ACE2016.
干预措施: Fludarabine (Drug)
ACE2016 ONLY: 3 DOSES
ACE2016 recommended dose, monotherapy. Lymphodepleting regimen followed by recommended dose of ACE2016.
干预措施: ACE2016 (Drug)
ACE2016 AND PEMBROLIZUMAB: 3 DOSES
ACE2016 recommended dose, in combination with pembrolizumab. Lymphodepleting regimen followed by recommended dose of ACE2016, giving in combination with pembrolizumab.
干预措施: Cyclophosphamide (Drug)
ACE2016 AND PEMBROLIZUMAB: 3 DOSES
ACE2016 recommended dose, in combination with pembrolizumab. Lymphodepleting regimen followed by recommended dose of ACE2016, giving in combination with pembrolizumab.
干预措施: Fludarabine (Drug)
ACE2016 AND PEMBROLIZUMAB: 3 DOSES
ACE2016 recommended dose, in combination with pembrolizumab. Lymphodepleting regimen followed by recommended dose of ACE2016, giving in combination with pembrolizumab.
干预措施: ACE2016 (Drug)
结局指标
主要结局
Incidence of DLTs, AESIs, Grade 3 or higher TEAEs, TEAEs considered related to ACE2016, TEAEs resulting in death, SAEs, related SAEs, and TEAEs leading to treatment discontinuation will be summarized by cohort
时间窗: 1 year
Change from baseline in clinical laboratory tests results
时间窗: 1 year
Number of subject with change from baseline clinical significant lab findings by cohort (descriptive)
Change from baseline in vital signs results
时间窗: 1 year
Number of subjects with change from baseline clinical significant vital signs findings by cohort (descriptive)
Recommended Dose (RD)
时间窗: 1 year
次要结局
- Progression Free Survival (PFS)(1 year)
- Duration Of Response (DOR)(1 year)
- Persistence of ACE2016 before and after administration(1 year)
- Objective Response Rate (ORR)(1 year)
- Measure of anti-ACE2016 antibodies after administration(1 year)
- Disease Control Rate (DCR)(1 year)