A Phase I Clinical Study of IX001 TCR-T Injection in the Treatment of Advanced Pancreatic Cancer Patients With KRAS G12V Mutation

1\. The subject is currently suffered from or have suffered from other incurable malignant tumors within previous 5 years, except in skin basal cell cancer、carcinoma in situ or breast cancer have received curative treatment with no recurrence within the past 3 years)

2\. History of organ transplantation

3\. A history of mental disorders, which may affect compliance with this protocol or lead to failure in signing the Informed Consent Forms(ICF)

4\. A history of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus) requiring systemic immunosuppressive/systemic disease-modulating drugs

5\. Poorly controlled hypertension with drug (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg) or occurrence of grade III-IV heart failure or myocardial infarction, cardiac angioplasty or stent placement, unstable angina pectoris, or other clinically significant heart diseases within one year prior to signing the ICF; QTc interval \>450 ms for males or QTc interval \>470 ms for females during screening (QTc interval calculated using the Fridericia formula)

6\. Symptomatic intracranial metastases

7\. Subjects have ascites or pleural effusion requiring drainage to relieve symptoms or have received drainage within 2 weeks. Asymptomatic participants with a small amount of pleural effusion or ascites on imaging are allowed

8\. Subjects who have experienced tumor-related intestinal or bowel obstruction within 6 months. including incomplete obstruction related to underlying disease or symptoms of intestinal obstruction requiring treatment

9\. A history of or any central nervous system disorders, such as epileptic seizure, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system within the past 6 months

10\. A positive result obtained in any of the following virological tests: A) Antibody to human immunodeficiency virus (HIV antibody); B) Hepatitis C virus antibody (HCV antibody), with a positive result for hepatitis C virus ribonucleic acid (HCV RNA); C) Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV DNA) copies ≥2000 IU/mL; D) Treponema pallidum antibody (TP antibody) and positive for unheated serum reagin test;

11\. Fungal, bacterial, viral or other infections or suspected fungal, bacterial, viral or other infections that cannot be controlled or require intravenous administration

12\. Significant tendency for bleeding, such as active gastrointestinal bleeding, coagulation disorders

13\. Deep vein thrombosis requiring treatment within the past 6 months, unless the risk of thrombosis is acceptable after treatment, as assessed by the investigator

14\. Interstitial lung disease (such as interstitial pneumonia, pulmonary fibrosis), or a history of clinically significant respiratory system diseases at screening

15\. Use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 2 weeks prior to leukapheresis

16\. Receipt of gene therapy or other cell therapies within the past 6 months

17\. Participation in any other clinical studies within 28 days prior to signing the master informed consent form, or the date of signing the master informed consent form still within 5 half-lives of the drug from the last dose in the last clinical study (whichever is longer)

18\. Patients with poor compliance due to physiological, family, social, geographic and other factors, and failure to follow the study protocol and the follow-up plan

19\. Patients with contraindications to drugs used in the study

20\. Comorbidities requiring treatment with systemic corticosteroids (dexamethasone at a dose of ≥ 5 mg/day or other corticosteroids at the equivalent dose) or other immunosuppressive drugs after initiation of the study treatment, as judged by the investigator

21\. Women who are breastfeeding and are unwilling to stop breastfeeding

22\. Any other conditions that are, in the opinion of the investigator, not suitable for enrollment

What this study is about