A Phase I Trial to Evaluate the Safety of IMC002 in Advanced Digestive System Tumors

Inclusion Criteria:

• Willing and able to provide signed and dated informed consent prior to anystudy-related procedures and willing and able to comply with all study procedures
• Age > 18 and ≤70 years
• Patients with histologically or cytologically confirmed locally advanced/metastaticdigestive system tumors including but not limited to advanced gastric cancer at leastfailed two lines of SOC, esophagogastric junction adenocarcinoma, and advancedpancreatic cancer failed at least one line SOC;
• Must have CLDN18.2 positive tumor expression histologically as determined by IHC (defined as positive rate of tumor cells≥40% and staining intensity ≥2+ ) or a biopsyif archived tumor sample is not available; representative tumor samples (primary ormetastatic, archived or newly collected) are expected to be obtained
• Expected survival time ≥12 weeks
• Measurable or evaluable disease per RECIST1.1
• ECOG performance status score of 0-1
• Adequate organ and bone marrow function. If any laboratory test results are abnormalwith reference to the criteria below, a repeat test can be performed within 1 week. Ifthe test results are still abnormal, the patient fails screening.
• Recovery to grade 0-1 from AEs related to prior anticancer therapy or to an acceptablelevel for inclusion/exclusion criteria except alopecia and vitiligo
• Female of childbearing age must undergo a serum pregnancy test with negative resultsat screening and infusion; Female of childbearing age or male patients whose sexualpartners are females of childbearing age are willing to take medically approvedhigh-efficiency contraceptive measures such as intrauterine devices or condoms fromthe time of signing the informed consent to 1 year after infusion (women ofchildbearing age include premenopausal women and women within 24 months of postmenopause).

Exclusion Criteria:

• Pregnant and lactating women
• Human immunodeficiency virus (HIV) antibody positive; acute or chronic activehepatitis B; acute or chronic active hepatitis C Hepatitis. Syphilis antibodypositive; cytomegalovirus (CMV) infection; Epstein-Barr (EB) virus infection.
• Active or clinically poorly controlled serious infections
• Uncontrollable pleural effusion, pericardial effusion and ascites effusion existedbefore enrollment.
• Extensive or diffuse lung or liver metastases
• Oxygen saturation ≤95% without oxygen inhalation
• With other diseases that may limit their participation in this study, such aspulmonary embolism, chronic obstructive pulmonary disease, symptomatic or poorlycontrolled interstitial lung disease, or clinically significant abnormal lung functiontests
• Known prior or current hepatic encephalopathy requiring treatment; patients withcurrent or history of central nervous system (CNS) disease. Autoimmune diseases; CNSmetastases or meningeal metastases with clinical symptoms, or other evidence that thepatient's CNS or meningeal metastases have not been controlled, and are judged notsuitable for the study by the investigator
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic bloodpressure > 100 mmHg after standardized antihypertensive drug treatment); not wellcontrolled diabetes mellitus [fasting plasma glucose (FPG) ≥10.2mmol/L].
• Presence of any of clinical cardiac symptoms or disorders
• Evidence of major coagulopathy or other significant bleeding risk
• Systemic steroids equivalent to >15mg/day prednisone within 2 weeks beforeleukapheresis, except inhaled or topic steroids
• Requiring systemic therapy with corticosteroids or other immunosuppressive drugsduring the treatment period. Presence of any active autoimmune disease, or history ofautoimmune disease expect recur.
• Previous or concomitant other malignancies
• Have received other gene therapies including but not limited to any CAR-T and TCR-Ttherapy
• Anti-tumor therapies other than for the pretreatment and bridging therapies < 5half-lives or 28 days (whichever is shorter) prior to study treatment
• Any investigational drugs or study drugs from a previous clinical study within 30 daysprior to signing the informed consent; traditional Chinese medicine with anti-tumoractivities within 2 weeks prior to the study treatment
• History of serious allergic disease or known allergy to any component of the studytreatments
• With severe mental disorders
• Any issue that would impair the ability of the patient to receive or tolerate theplanned treatment, to understand informed consent or any condition for which, in theopinion of the investigator, participation would not be in the best interest of thepatient (e.g., compromise the well-being) or that could prevent, limit, or confoundthe protocol-specified assessments.