A Phase 1, First in Human Study of Adenovirally Transduced Autologous Macrophages Engineered to Contain an Anti-HER2 Chimeric Antigen Receptor in Subjects With HER2 Overexpressing Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 48
- 试验地点
- 7
- 主要终点
- Assess the safety and tolerability of CT-0508 in combination with pembrolizumab by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors (CT-0508 and pembrolizumab substudy only)
研究概览
简要总结
Phase 1, first-in-human, open label study of CAR macrophages in HER2 overexpressing solid tumors.
详细描述
A Phase 1, First in Human Study of Adenovirally Transduced Autologous Macrophages Engineered to Contain an Anti-HER2 Chimeric Antigen Receptor in Subjects with HER2 Overexpressing Solid Tumors
Main Study - Group 1 and Group 2 all HER2 overexpressing solid tumors
Intraperitoneal Substudy - HER2 overexpressing peritoneal disease
89[Zr] radiolabeled CT-0508 Substudy - All HER2 overexpressing solid tumors (Univ of Penn, Abramson Cancer Center only)
CT-0508 Combination with Pembrolizumab Substudy - All HER2 overexpressing solid tumors
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HER2-positive recurrent or metastatic solid tumors for which there are no available curative treatment options.
- •Breast cancer and gastric/gastroesophageal junction cancers must have failed approved HER2-targeted agents.
- •Other HER2-positive tumor types must have failed standard of care therapies, while prior therapy with anti-HER2 drugs is not required.
- •Subject must be willing and able to undergo tumor tissue biopsy procedures
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Subject has adequate bone marrow and organ function
排除标准
- •HIV, active hepatitis B or hepatitis C infection.
- •Diagnosis of immunodeficiency or chronic exposure to systemic corticosteroid therapy or any other form of immunosuppressive therapy
- •Untreated or symptomatic central nervous system (CNS) metastases or cytology proven carcinomatous meningitis.
- •o Subjects with small, asymptomatic CNS metastases that do not require treatment are permitted to enroll.
- •Left ventricular ejection fraction (LVEF) <50% as determined by ECHO or multiple gated acquisition scan (MUGA)
- •Other protocol-defined Inclusion/Exclusion may apply.
- •CT-0508 in Combination with Pembrolizumab Substudy Only:
- •Exclusion Criteria:
- •Subjects with severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
- •Subjects with an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- •Subjects who have a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Subjects who have had an allogeneic tissue/solid organ transplant
研究组 & 干预措施
Group 1 and Group 2
Both groups will receive the full dose manufactured per patient. Group 1 will undergo intra subject dose escalation of IV administrations of up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5. Group 2 will receive the full dose IV on Day 1 of up to 5 billion cells total.
干预措施: CT-0508 (Biological)
Intraperitoneal Administration
All cohorts will receive the full dose manufactured per patient. Cohorts 1-3 will undergo intrasubject dose escalations of IP administration as follows:
Cohort 1 up to 500 million total cells on Day 1, up to 1 billion total cells on Day 3 and up to 1.5 billion total cells on Day 5.
Cohort 2 up to 1.5 billion total cells on Day 1, up to 2 billion total cells on Day 3 and any remaining cells on Day 5.
Cohort 3 up to 2.5 billion total cells on Day 1 and up to 2.5 billion total cells on Day 3.
Cohort 4 will 1 dose on Day 1 of up to 5 billion total cells.
干预措施: CT-0508 (Biological)
89[Zr]radiolabeled CT-0508
89[Zr] radiolabeled group will receive a full dose IV on Day 1 of up to 500 million total cells of 89[Zr] radiolabeled CT-0508 and non-radiolabeled CT-0508 of up to 4.5 billion total cells (Univ of Penn Abramson Cancer Center only).
干预措施: CT-0508 (Biological)
CT-0508 in Combination with Pembrolizumab
All regimen levels will receive the full dose manufactured per patient up to 5 billion total cells. Regimen Levels 1 and 2 will undergo intrasubject dose escalations of IV administration as follows:
Regimen Level 1: up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5 plus pembrolizumab 200 mg q3w starting on Day 8.
Regimen Level 2: up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5 plus pembrolizumab 200 mg q3w starting on Day 1.
Regimen Level 3 will receive the full dose IV on Day 1 of up to 5 billion total cells plus pembrolizumab 200 mg q3w starting on Day 1.
干预措施: CT-0508 (Biological)
CT-0508 in Combination with Pembrolizumab
All regimen levels will receive the full dose manufactured per patient up to 5 billion total cells. Regimen Levels 1 and 2 will undergo intrasubject dose escalations of IV administration as follows:
Regimen Level 1: up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5 plus pembrolizumab 200 mg q3w starting on Day 8.
Regimen Level 2: up to 500 million total cells on Day 1, up to 1.5 billion total cells on Day 3, and up to 3.0 billion total cells on Day 5 plus pembrolizumab 200 mg q3w starting on Day 1.
Regimen Level 3 will receive the full dose IV on Day 1 of up to 5 billion total cells plus pembrolizumab 200 mg q3w starting on Day 1.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Assess the safety and tolerability of CT-0508 in combination with pembrolizumab by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors (CT-0508 and pembrolizumab substudy only)
时间窗: 14 months
Frequency and severity of adverse events including, but not limited to, estimating frequency and severity of Cytokine Release Syndrome (CRS)
Assess the safety and tolerability of CT-0508 by estimating the frequency and severity of adverse events in subjects with HER2 overexpressing solid tumors.
时间窗: 14 months
Frequency and severity of adverse events including, but not limited to, estimating frequency and severity of Cytokine Release Syndrome (CRS)
Assess the feasibility of manufacturing CT-0508 by describing the percentage of products passing release criteria.
时间窗: 12 months
Percentage of products that pass release criteria among all manufactured products.
次要结局
- Estimate the objective response rate (ORR), according to RECIST v1.1, of at least 1 dose of CT-0508 among subjects with HER2 overexpressing solid tumors.(24 months)
- Estimate progression-free survival (PFS).(24 months)