A Phase 1 Dose Escalation Study To Assess Safety And Efficacy Of ADP-A2M4CD8 As Monotherapy Or In Combination With Either Nivolumab Or Pembrolizumab In HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- USWM CT, LLC
- 入组人数
- 120
- 试验地点
- 17
- 主要终点
- To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab
研究概览
简要总结
This study will investigate the safety and tolerability of ADP-A2M4CD8 T-cell therapy in subjects who have the appropriate human leukocyte antigen (HLA) and MAGE-A4 tumor antigen. Tumor indications include endometrial, esophageal, esophagogastric junction (EGJ), gastric, head and neck, melanoma, non-small cell lung (NSCLC), ovarian or urothelial cancer.
详细描述
Conditions:
Endometrial Esophageal Cancer Esophagogastric Junction (EGJ) Gastric (stomach) Head and Neck Melanoma Non-small Cell Lung (NSCLC) Ovarian Cancer
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
- •Key Inclusion criteria
- •Age ≥18 and ≤ 75 years
- •Subject is positive for at least 1 HLA-A*02 inclusion allele
- •Histologically or cytogenetically confirmed diagnosis of urothelial cancer, esophageal, esophagogastric junction (EGJ) cancer, gastric cancer, non-small cell lung carcinoma (NSCLC), head and neck or ovarian cancer, endometrial cancer, melanoma
- •Measurable disease according to RECIST v1.1 prior to leukapheresis and lymphodepletion.
- •Tumor shows MAGE-A4 expression as confirmed by central laboratory
- •ECOG Performance Status of 0 or
- •Left ventricular ejection fraction (LVEF) ≥50% or the institutional lower limit of normal range, whichever is lower Note: other protocol defined Inclusion/
排除标准
- •Subjects must have ≥ 90% room air oxygen saturation at rest at Screening (within 7 days of leukapheresis) and at Baseline.
- •Key exclusion criteria
- •Positive for any HLA-A*02 allele other than: one of the inclusion alleles
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study
- •Active autoimmune or immune mediated disease
- •Leptomeningeal disease, carcinomatous meningitis or symptomatic CNS metastases
- •Other prior malignancy that is not considered by the Investigator to be in complete remission. Clinically significant cardiovascular disease
- •Uncontrolled intercurrent illness
- •Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
- •Pregnant or breastfeeding
- •Note: other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Autologous genetically modified ADP-A2M4CD8 cells
干预措施: Autologous genetically modified ADP-A2M4CD8 cells alone or in combination with nivolumab every four weeks or pembrolizumab every 6 weeks (Genetic)
结局指标
主要结局
To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab
时间窗: 2.5 years
Determination of incidence of dose-limiting toxicities, adverse events and tolerable dose
To evaluate safety of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab
时间窗: Up to 15 years
Incidence of patients with Replication-competent Retrovirus, persistence of ADP-A2M4CD8 T-cells and incidence of insertional oncogenesis.
次要结局
- Time to response (TTR)(2.5 years)
- Anti-tumour activity: Overall Response Rate (ORR)(2.5 years)
- Anti-tumor activity: Best overall response (BOR)(2.5 years)
- Duration of Response (DOR)(2.5 years)
- Duration of stable disease (DoSD)(2.5 years)
- Overall Survival (OS)(15 years)
- Progression Free Survival (PFS)(2.5 years)