Open-label, Phase 1, Multi-Center Master Protocol to Evaluate the Safety and Preliminary Anti-Tumor Activity of TCR-engineered T Cells Recognizing KRAS Mutations in Adult Subjects With Unresectable, Advanced, and/or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 108
- 试验地点
- 19
- 主要终点
- Part A (Dose Escalation): Evaluate the safety of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors
研究概览
简要总结
Phase I Study, a master protocol to investigate TCR-Engineered T cells recognizing KRAS mutations in adult subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors.
详细描述
This is a Phase 1, open-label, Phase 1, Multi-Center Master Protocol to evaluate the safety and preliminary Anti-Tumor activity of TCR-Engineered T cells (KRAS TCRTs) recognizing KRAS mutations in adult subjects with Unresectable, Advanced, and/or Metastatic Solid Tumors.
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
- •Age ≥18 years
- •Diagnosed with NSCLC, Colorectal adenocarcinoma, Pancreatic adenocarcinoma, Endometrial Cancer or any other solid tumor
- •Tumors must harbor a KRAS G12D variant mutation and subject must be HLA-C*08:02 positive, HLA-A*11:01 or HLA-A*11:02 positive in at least one allele
- •Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease (Stage III or IV) after at least 1 line of approved systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options.
- •Presence of at least 1 measurable lesion per RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the time of enrollment
排除标准
- •Any other primary malignancy within the 3 years prior to enrollment (except for non-melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast) or low-grade prostate cancer
- •Known, active primary central nervous system (CNS) malignancy
- •History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.
- •History of stroke or transient ischemic attack within the 12 months prior to enrollment.
- •History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment.
- •Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment.
- •Any form of primary immunodeficiency.
- •Active immune-mediated disease requiring systemic steroids or other immunosuppressive treatment (except if related to prior checkpoint inhibitor therapy)
- •Female of childbearing potential who is lactating or breast feeding at the time of enrollment
- •Prior treatment with pan-KRAS or KRAS G12D targeting agents unless presence of KRAS G12D mutation is confirmed after the completion of treatment with pan-KRAS or KRAS G12D targeting agents.
研究组 & 干预措施
NT-112
Part A Dose Escalation and Part B Dose Expansion of NT-112
干预措施: NT-112: Autologous, engineered T Cells targeting KRAS G12D (Biological)
AZD0240
Part A Dose Escalation and Part B Dose Expansion of AZD0240
干预措施: AZD0240: Autologous, engineered T Cells targeting KRAS G12D (Biological)
结局指标
主要结局
Part A (Dose Escalation): Evaluate the safety of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors
时间窗: Through study completion, an average of 2 years
Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Part A (Dose Escalation): Evaluate MTD and recommended dose for expansion (RDE)
时间窗: 28 days after infusion
Incidence of DLTs, treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Part B (Expansion): Further evaluate the safety of KRAS TCRTs at the RDE in subjects with unresectable, advanced, and/or metastatic solid tumors
时间窗: 28 days after infusion
Incidence of DLTs, treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs)
次要结局
- Part A (Dose Escalation): Evaluate the preliminary anti-tumor activity of KRAS TCRTs in subjects with unresectable, advanced, and/or metastatic solid tumors(Up to 24 months post-infusion)
- Part B (Dose Expansion): Evaluate the preliminary anti-tumor activity of KRAS TCRTs at the RDE in subjects with unresectable, advanced, and/or metastatic solid tumors(Up to 24 months post infusion)