An Exploratory Study on the Safety and Efficacy of CRTKVA11-03 TCR-T Cell Injection in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- DLT (Dose Limiting Toxicity) Incidence Rate
研究概览
简要总结
This is a single-center, open-label, single-arm, dose-escalation study aimed at evaluating the safety and preliminary efficacy of KRAS-specific autologous TCR-T cells in patients with advanced solid tumors harboring KRAS G12V mutation.
详细描述
CRTKVA11-03 injection was developed based on affinity-optimized KRAS G12V-specific TCR molecules. Its safety and tolerability was explored in a single-center, open-label, single-arm, dose-escalation study. 9 - 18 patients with advanced solid tumors who have KRAS G12V mutation and HLA-A*11:01 genotype, and have failed standard treatments will be treated wtith CRTKVA11-03 TCR-T injection. The primary objective is to evaluate the safety and tolerability of CRTKVA11-03 in the treatment of advanced malignant solid tumors, the secondary objective is to describe the pharmacokinetic (PK) characteristics of CRTKVA11-03 after infusion into humans, observe their proliferation and persistence in vivo. The key study procedures include leucocyte apheresis and preparation of TCR-T cells, lymphocyte depletion (lymphodepletion), and the infusion of CRTKVA11-03 injection and follow-up.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18-70 years.
- •Histologically or cytologically confirmed advanced solid tumors (e.g., colorectal cancer, pancreatic cancer, NSCLC) with KRAS G12V mutations and HLA-A*11:01 genotype.
- •Failed standard therapies or no effective treatment available.
- •ECOG performance status of 0-
- •Life expectancy of ≥3 months.
- •Presence of at least one measurable lesion as defined by RECIST 1.1 criteria.
- •Female patients of childbearing potential must agree to use highly effective contraceptive methods during the study and for at least 6 months after the last dose. A negative pregnancy test within 7 days prior to treatment initiation is required.
- •Written informed consent provided by the patient, with an expectation of compliance with study procedures.
排除标准
- •Prior treatment with gene-modified T-cell therapies.
- •Current treatment with T-cell suppressive agents (e.g., cyclophosphamide, FK506, tripterygium glycosides) or T-cell stimulants.
- •Chemotherapy, targeted therapy, immunotherapy, or investigational drugs administered within 2 weeks, or radiotherapy within 4 weeks prior to enrollment.
- •Significant organ dysfunction, as evidenced by:
- •leukocytes<3.0 x 109/L
- •absolute neutrophil count >1.5 x 109/L
- •hemoglobin<90g/L
- •platelets <100 x 109/L
- •Creatinine>1.5×ULN or creatinine clearance <50mL/min
- •lymphocytes<0.5 x 109/L
- •total bilirubin>3×ULN; ALT/AST>3×ULN (or >5× ULN in patients with liver metastases)
- •INR/APTT>1.5×ULN
- •Presence of serious diseases and comorbidities, including but not limited to: severe heart disease, cerebrovascular disease, seizures, poorly controlled diabetes (such as Type 1 diabetes or insulin-dependent diabetes), pancreatic dysfunction, severe infections, active gastrointestinal ulcers, gastrointestinal bleeding, mechanical or paralytic bowel obstruction, pulmonary fibrosis, renal failure, respiratory failure, etc.
- •History of severe cardiovascular diseases within the past 6 months, including but not limited to: myocardial infarction, severe or unstable angina, coronary artery or peripheral artery bypass surgery, New York Heart Association (NYHA) Class III or IV heart failure, etc.
- •Left ventricular ejection fraction (LVEF) < 50%.
- •Symptomatic brain metastases unless stabilized with prior treatment (e.g., surgery or radiotherapy).
- •Known history of myelodysplastic syndrome, lymphoma, or other malignancies.
- •Known allergy to albumin, investigational drugs, or their excipients.
- •Active autoimmune diseases, including but not limited to acquired/congenital immunodeficiency, organ transplantation, autoimmune hepatitis, systemic lupus erythematosus, or inflammatory bowel disease.
- •Active hepatitis B, hepatitis C, or HIV infection.
- •Pregnancy or breastfeeding.
- •Uncontrolled mental or neurological disorders.
- •Any condition deemed unsuitable for study participation by the investigator.
研究组 & 干预措施
CRTKVA11-03 TCR-T Cell Injection
CRTKVA11-03 TCR-T Cell Injection (5×10⁹, 1×10¹°, or 2×10¹° TCR-T cells per dose) with preconditioning lymphodepletion using Fludarabine and Cyclophosphamide, followed by IL-2 support
干预措施: CRTKVA11-03 TCR-T Cell Injection (Drug)
结局指标
主要结局
DLT (Dose Limiting Toxicity) Incidence Rate
时间窗: 28 days
Explore the MTD (Maximum Tolerated Dose) or Subsequent Expansion Dose
时间窗: 28 days
Safety Assessment: Changes in patient safety parameters at various follow-up time points after TCR-T infusion, as well as the incidence of adverse events (AEs), which were graded according to the CTCAE V6.0 severity scale.
时间窗: 2 years
次要结局
- Disease Control Rate (DCR) Assessed by RECIST 1.1(2 years)
- Duration of Response (DOR) Assessed by RECIST 1.1(2 years)
- Objective Response Rate (ORR) Assessed by RECIST 1.1(2 years)
- Progression-Free Survival (PFS) Assessed by RECIST 1.1(2 years)
- Overall Survival (OS)(2 years)
- qPCR Monitoring of TCR-T Cell Copy Numbers in Peripheral Blood(2 years)