Overview

This is a single-arm, open-label clinical study to evaluate the safety, tolerability and preliminary efficacy of IX001 TCR-T injection in advanced pancreatic cancer patients with KRAS G12V mutation.

Eligibility

Inclusion Criteria:

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1. Voluntary signing of an informed consent form (for Human Leukocyte Antigen (HLA) typing and tumor gene mutation test, and main screening)

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2. Males or females, aged 18-75 years (inclusive)

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       3. Patients with pathologically (histopathologically) or cytologically confirmed
          pancreatic ductal adenocarcinoma

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       4. Patients with unresectable locally advanced or metastatic disease who fail
          standard of care, i.e., patients who have progression after prior
          gemcitabine-containing chemotherapy or FOLFIRINOX (oxaliplatin + irinotecan +
          calcium folinate + 5-FU) or NALIRIFOX (irinotecan liposome + oxaliplatin +
          calcium folinate + 5-FU) regimen, including those who have progression within 6
          months after the end of neoadjuvant/adjuvant therapy

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       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 mm for lymph node lesions (tumor lesions situated in a
          previously irradiated area, or in an area subjected to other loco-regional
          therapy, are usually not considered measurable, unless unequivocal progression
          of the lesion is demonstrated by an evidence)

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       6. Patients with tumor tissue or peripheral blood tested positive for KRAS-G12V
          mutation and expression of matching HLA-A*11:01 subtype

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7. Eastern Cooperative Oncology Group (ECOG) ≤ 1

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8. Life expectancy ≥3 months

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       9. Adequate functional reserve of organs: A) Hematology requirements (no blood
          transfusion or hematopoietic stimulating factor treatment within 14 days):
          Absolute neutrophil 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: Alanine aminotransferase ≤ 3 × upper limit of normal（ULN） (≤ 5 ×
          ULN for patients with liver metastases); Aspartate aminotransferase ≤ 3 × ULN
          (≤ 5 × ULN for patients with liver metastases); Creatinine ≤ 1.5 × ULN or
          creatinine clearance ≥ 50 mL/min; Serum total bilirubin ≤ 1.5 × ULN; C)
          Coagulation requirements: Partial thromboplastin activity time (APTT) ≤ 1.5 ×
          ULN; International normalized ratio (INR) ≤1.5 × ULN; D) Left ventricular
          ejection fraction (LVEF) ≥ 50% and no clinically significant pericardial
          effusion as diagnosed by echocardiography; E) No clinically significant
          electrocardiographic abnormality; F) Basic oxygen saturation is >92% under the
          indoor natural air environment.

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      10. Women of childbearing age must be negative for blood Human Chorionic
          Gonadotropin (HCG) pregnancy test (by immunofluorescence method) at screening
          and baseline periods, and agree to use effective contraception for at least 1
          year after infusion; and male subjects whose partners are women of childbearing
          age must agree to use effective barrier contraception methods and avoid sperm
          donation for at least 1 year after infusion.

Exclusion Criteria:

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1. Other malignancies (except non-melanoma skin cancer with the disease-free survival of more than 5 years and cervical carcinoma in situ, bladder cancer, or breast cancer)

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2. History of organ transplantation

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

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

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       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)

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       6. Presence of any indwelling catheter or drainage tube (e.g., percutaneous
          nephrostomy tube, indwelling catheter, bile drainage tube or
          pleural/peritoneal/pericardial catheter), except any dedicated central venous
          catheter

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       7. Symptomatic intracranial metastases, or moderate to severe ascites or pleural
          effusion requiring drainage to relieve symptoms

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       8. 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

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       9. 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;

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

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

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

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

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

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

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      16. 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)

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      17. 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

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18. Patients with contraindications to drugs used in the study

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      19. 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

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20. Women who are breastfeeding and are unwilling to stop breastfeeding

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