CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* 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 0-1.
* 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.

Exclusion Criteria:

* 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
  * SpO2≤93%
* 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.

主要终点：DLT (Dose Limiting Toxicity) Incidence Rate · 28 days；Explore the MTD (Maximum Tolerated Dose) or Subsequent Expansion Dose · 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. · 2 years
次要终点：Objective Response Rate (ORR) Assessed by RECIST 1.1；Disease Control Rate (DCR) Assessed by RECIST 1.1；Duration of Response (DOR) Assessed by RECIST 1.1；Progression-Free Survival (PFS) Assessed by RECIST 1.1；Overall Survival (OS)；qPCR Monitoring of TCR-T Cell Copy Numbers in Peripheral Blood

• CRTKVA11-03 TCR-T Cell Injection · EXPERIMENTAL · 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

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.