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

Inclusion Criteria:

• 1. Voluntary signing of an informed consent form (for Human Leukocyte Antigen (HLA)typing and tumor gene mutation test, and main screening)
• 2. Males or females, aged 18-75 years (inclusive)
• 3. Patients with pathologically (histopathologically) or cytologically confirmedpancreatic ductal adenocarcinoma
• 4. Patients with unresectable locally advanced or metastatic disease who failstandard of care, i.e., patients who have progression after priorgemcitabine-containing chemotherapy or FOLFIRINOX (oxaliplatin + irinotecan +calcium folinate + 5-FU) or NALIRIFOX (irinotecan liposome + oxaliplatin + calciumfolinate + 5-FU) regimen, including those who have progression within 6 months afterthe end of neoadjuvant/adjuvant therapy
• 5. At least one measurable lesion (according to RECIST 1.1 criteria), specifically:longest diameter of ≥10 mm for non lymph node lesions or shortest diameter of ≥15 mmfor lymph node lesions (tumor lesions situated in a previously irradiated area, orin an area subjected to other loco-regional therapy, are usually not consideredmeasurable, unless unequivocal progression of the lesion is demonstrated by anevidence)
• 6. Patients with tumor tissue or peripheral blood tested positive for KRAS-G12Vmutation and expression of matching HLA-A*11:01 subtype
• 7. Eastern Cooperative Oncology Group (ECOG) ≤ 1
• 8. Life expectancy ≥3 months
• 9. Adequate functional reserve of organs: A) Hematology requirements (no bloodtransfusion or hematopoietic stimulating factor treatment within 14 days): Absoluteneutrophil count ≥ 1.5×10^9/L; Platelet count ≥ 75×10^9/L, hemoglobin > 90 g/dL;Absolute lymphocyte count ≥ 0.5×10^9/L; B) Blood Biochemistry Requirements: Alanineaminotransferase ≤ 3 × upper limit of normal（ULN） (≤ 5 × ULN for patients with livermetastases); Aspartate aminotransferase ≤ 3 × ULN (≤ 5 × ULN for patients with livermetastases); Creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min; Serum totalbilirubin ≤ 1.5 × ULN; C) Coagulation requirements: Partial thromboplastin activitytime (APTT) ≤ 1.5 × ULN; International normalized ratio (INR) ≤1.5 × ULN; D) Leftventricular ejection fraction (LVEF) ≥ 50% and no clinically significant pericardialeffusion as diagnosed by echocardiography; E) No clinically significantelectrocardiographic abnormality; F) Basic oxygen saturation is >92% under theindoor natural air environment.
• 10. Women of childbearing age must be negative for blood Human ChorionicGonadotropin (HCG) pregnancy test (by immunofluorescence method) at screening andbaseline periods, and agree to use effective contraception for at least 1 year afterinfusion; and male subjects whose partners are women of childbearing age must agreeto use effective barrier contraception methods and avoid sperm donation for at least 1 year after infusion.

Exclusion Criteria:

• 1. The subject is currently suffered from or have suffered from other incurablemalignant tumors within previous 5 years, except in skin basal cell cancer、carcinomain situ or breast cancer have received curative treatment with no recurrence withinthe past 3 years)
• 2. History of organ transplantation
• 3. A history of mental disorders, which may affect compliance with this protocol orlead to failure in signing the Informed Consent Forms(ICF)
• 4. A history of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis andsystemic lupus erythematosus) requiring systemic immunosuppressive/systemicdisease-modulating drugs
• 5. Poorly controlled hypertension with drug (systolic blood pressure >160 mmHgand/or diastolic blood pressure >100 mmHg) or occurrence of grade III-IV heartfailure or myocardial infarction, cardiac angioplasty or stent placement, unstableangina pectoris, or other clinically significant heart diseases within one yearprior to signing the ICF; QTc interval >450 ms for males or QTc interval >470 ms forfemales during screening (QTc interval calculated using the Fridericia formula)
• 6. Symptomatic intracranial metastases
• 7. Subjects have ascites or pleural effusion requiring drainage to relieve symptomsor have received drainage within 2 weeks. Asymptomatic participants with a smallamount of pleural effusion or ascites on imaging are allowed
• 8. Subjects who have experienced tumor-related intestinal or bowel obstructionwithin 6 months. including incomplete obstruction related to underlying disease orsymptoms 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 autoimmunedisease 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 virusantibody (HCV antibody), with a positive result for hepatitis C virus ribonucleicacid (HCV RNA); C) Positive for hepatitis B surface antigen (HBsAg); or positive forhepatitis B core antibody (HBcAb) and positive for hepatitis B virusdeoxyribonucleic 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 intravenousadministration
• 12. Significant tendency for bleeding, such as active gastrointestinal bleeding,coagulation disorders
• 13. Deep vein thrombosis requiring treatment within the past 6 months, unless therisk 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-macrophagecolony-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 themaster informed consent form, or the date of signing the master informed consentform still within 5 half-lives of the drug from the last dose in the last clinicalstudy (whichever is longer)
• 18. Patients with poor compliance due to physiological, family, social, geographicand 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 (dexamethasoneat a dose of ≥ 5 mg/day or other corticosteroids at the equivalent dose) or otherimmunosuppressive drugs after initiation of the study treatment, as judged by theinvestigator
• 21. Women who are breastfeeding and are unwilling to stop breastfeeding
• 22. Any other conditions that are, in the opinion of the investigator, not suitablefor enrollment