Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 10
- 主要终点
- Incidence of Treatment Emergent Adverse Events
研究概览
简要总结
This study is open to adult patients with solid tumors who have a KRAS G12V mutation. This mutation is often found in non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) and other cancers. The study is for patients whose cancer has spread through the body and for whom previous treatments were not successful or treatment does not exist. Patients must also be positive for HLA-A*11:01. The purpose of this study is to find the best dose of AFNT-211 that is safe and can shrink tumors in patients. AFNT-211 is an investigational therapy and this is the first time that AFNT-211 is being administered to patients. AFNT-211 is an autologous T cell product which means that it is made from a patient's own T cells. These cells are engineered and grown to recognize the KRAS G12V protein on the cell surface of cancer cells. AFNT-211 is infused into patients after a short course of lymphodepleting chemotherapy. Patients will frequently visit the study site. The doctors there will regularly check the size of the cancer and the patient's health. They will also take note of any unwanted effects. Patients may continue in this study for as long as they benefit from the treatment.
详细描述
AFNT-211 is a cellular therapy consisting of autologous CD4+ and CD8+ T cells engineered to express a human leukocyte antigen-A (HLA-A)*11:01-restricted Kirsten rat sarcoma (KRAS) G12V-specific transgenic T cell receptor (TCR), the wildtype CD8α/β coreceptor, and a FAS-41BB switch receptor. AFNT-211 is being developed by Affini-T Therapeutics, Inc. (hereafter, "the Sponsor") for the treatment of patients with malignant solid tumors. The primary purpose of this study is to assess the safety and tolerability of AFNT-211 in subjects who are HLA-A*11:01 positive with advanced or metastatic cancers that harbor a KRAS G12V mutation, as well as determine the optimal biological dose (OBD) and recommended Phase II dose (RP2D) of AFNT-211 in this population. This study will also evaluate the preliminary anti-tumor activity of AFNT-211.
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
- •Confirmed KRAS G12V mutational status and HLA-A*11:01 allele
- •Histologically confirmed advanced or metastatic, unresectable solid tumor
- •Progressed on or intolerant of at least one prior line of standard systemic therapy for the current malignancy.
- •Measurable disease per RECIST v1.
- •ECOG performance status 0-1
- •Adequate organ and bone marrow function
排除标准
- •Any systemic cytotoxic chemotherapy, investigational agents, or any anti-tumor drug from a previous treatment regimen or clinical study (including small molecules and I/O compounds) within 5 half-lives or 14 days of Screening, whichever is shorter.
- •Any prior gene therapy utilizing an integrating vector
- •Previous allogeneic stem cell transplantation or prior organ transplantation
- •History of treated primary immunodeficiency, autoimmune, or inflammatory disease including inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, or Grave's disease
- •Primary brain tumor
- •Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression.
- •Uncontrolled active bacterial, viral, fungal, or mycobacterial infection
- •Pregnant or lactating subjects
- •Surgery or catheter-based interventions
- •Previously identified allergy, hypersensitivity, or known contraindication to cyclophosphamide, fludarabine, or any other agent associated with lymphodepleting chemotherapy (LDC) or AFNT-211 product
- •Uncontrolled significant intercurrent or recent illness
- •Diagnosis of another malignancy within 2 years prior to screening.
- •Seropositive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb)
- •Seropositive for hepatitis C antibody.
- •Known human immunodeficiency virus (HIV) infection
研究组 & 干预措施
Dose Expansion: NSCLC
20 subjects with non-small cell cancer will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.
干预措施: AFNT-211 (Drug)
Dose Escalation
Subjects will be given a one-time infusion of AFNT-211 starting at dose level 1 and monitored for 28 days (DLT period). Each cohort will enroll 2-4 subjects at different dose levels for a total of 20 subjects in the escalation portion. The optimal biological dose and recommended phase 2 dose will be determined.
干预措施: AFNT-211 (Drug)
Dose Expansion: PDAC
20 subjects with pancreatic ductal adenocarcinoma will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.
干预措施: AFNT-211 (Drug)
Dose Expansion: CRC
20 subjects with colorectal carcinoma will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.
干预措施: AFNT-211 (Drug)
Dose Expansion: Adv Solid Tumors
20 subjects with solid tumors will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.
干预措施: AFNT-211 (Drug)
结局指标
主要结局
Incidence of Treatment Emergent Adverse Events
时间窗: 60 months
The incidence of TEAEs will be used to determine safety and tolerability of AFNT-211
Determine the Recommended Phase 2 Dose
时间窗: 60 months
This will be selected based on Bayesian optimal interval Phase I/II (BOIN12) design recommendation and the totality of benefit-risk evidence during dose escalation
Incidence of Dose Limiting Toxicities
时间窗: 18 months
The incidence of DLTs during Dose Escalation will be used to determine safety and tolerability of AFNT-211
Determine the Optimal Biological Dose (OBD)
时间窗: 60 months
Quantify the desirability of a dose in terms of toxicity-efficacy tradeoff during the dose escalation portion of the study
Incidence of Serious Adverse Events
时间窗: 60 months
The incidence of SAEs will be used to determine safety and tolerability of AFNT-211
次要结局
- Overall Survival (OS)(60 months)
- Progression-free Survival (PFS)(60 months)
- Clinical Benefit Rate (CBR)(60 months)
- Time to Response (TTR)(60 months)
- Overall Response Rate (ORR)(60 months)
- Duration of Response (DOR)(60 months)