SND002 Cell Injection in Participants With Advanced Malignant Solid Tumors

• Provision of written informed consent before any study-specific procedure, and ability to complete the study procedures and follow-up assessments.
• Age 18 to 80 years inclusive at the time of informed consent. Participants older than 80 years may be enrolled at the joint discretion of the investigator and the sponsor.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Part A (dose escalation): cytologically or histologically confirmed advanced malignant solid tumor, including but not limited to gastrointestinal tumors (colorectal, gastric, pancreatic, hepatic, and biliary tract), gynecologic tumors (cervical, ovarian, and endometrial), breast cancer, malignant melanoma, and lung cancer. Prior therapy must meet at least one of the following: (a) at least one line of systemic standard therapy for advanced or metastatic disease, with disease progression during or after the last dose, or intolerance (Grade 3 or higher irreversible toxicity); (b) no recognized standard treatment available as judged by the investigator; (c) inability to receive current standard treatment for specific reasons.
• Part B (expansion), cohort 1 (colorectal cancer): at least two lines of prior systemic standard therapy, including a fluoropyrimidine plus oxaliplatin and/or irinotecan, with or without targeted therapy (bevacizumab or cetuximab) and with or without immunotherapy (programmed cell death protein 1 or programmed death-ligand 1 inhibitors; microsatellite instability-high or mismatch repair-deficient tumors must have received this therapy), with disease progression or intolerance during or after the last dose.
• Part B, cohort 2 (gastric cancer): at least two lines of prior systemic standard therapy, including a platinum agent and/or a fluoropyrimidine, with or without immunotherapy (programmed cell death protein 1 or programmed death-ligand 1 inhibitors) and with or without a taxane; human epidermal growth factor receptor 2-positive tumors must have received anti-human epidermal growth factor receptor 2 therapy, with disease progression or intolerance during or after the last dose.
• Part B, cohort 3 (other solid tumors): tumors anticipated to respond based on dose-escalation data, potentially including malignant melanoma, pancreatic cancer, hepatic cancer, biliary tract cancer, cervical cancer, ovarian cancer, endometrial cancer, breast cancer, and lung cancer; at least one line of prior standard therapy according to the relevant guideline, with disease progression or intolerance during or after the last dose.
• Availability of at least one draining lymph node suitable for product manufacture, obtainable by conventional surgery or interventional procedure, or use of stored draining lymph node cells. Sentinel lymph node tissue is preferred when obtainable. The interval from prior radiotherapy or radiofrequency ablation to collection should preferably exceed 3 months.
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), excluding the lesion used for lymph node collection, which may serve only as a non-target lesion even if measurable.
• Life expectancy of at least 3 months.
• Adequate organ function, with laboratory results meeting all of the following within 14 days before enrollment and without platelet transfusion or colony-stimulating factor administration during that period:
• Absolute neutrophil count at least 1.0x10\^9/L.
• Platelet count at least 80x10\^9/L.
• Hemoglobin at least 80 g/L.
• Serum total bilirubin no more than 1.5 times the upper limit of normal (ULN); no more than 3 times ULN in participants with Gilbert syndrome or hepatic metastasis.
• Alanine aminotransferase and aspartate aminotransferase no more than 2.5 times ULN; no more than 5 times ULN in participants with hepatic metastasis.
• International normalized ratio no more than 1.5 times ULN and activated partial thromboplastin time no more than 1.5 times ULN, except in participants receiving anticoagulation.
• Creatinine clearance at least 60 mL/min calculated by the Cockcroft-Gault formula.
• Toxicities from prior therapy resolved to Grade 1 or lower before enrollment, except alopecia and Grade 2 or lower neuropathy caused by chemotherapy.
• Negative serum pregnancy test within 7 days before enrollment for women of childbearing potential. All participants of childbearing potential must agree to use effective contraception from enrollment until at least 6 months after SND002 Cell Injection infusion. A woman is considered not of childbearing potential if she meets at least one of the following: prior hysterectomy or bilateral oophorectomy; medically confirmed ovarian failure; medically confirmed physiological amenorrhea for at least 12 consecutive months, excluding chemotherapy, radiotherapy, or sex hormone therapy and other pathological causes.
• Ability to recognize and comply with the protocol as judged by the investigator.

Exclusion Criteria:

• More than 3 untreated central nervous system metastases at screening. Participants with 3 or fewer central nervous system metastases may be enrolled if the largest diameter is less than 1 cm, there is no peritumoral edema on brain imaging, and there is no evidence of progressive central nervous system disease on brain imaging at least 3 months after treatment.
• Prior adoptive cell therapy, including dendritic cells, cytokine-induced killer cells, T cells, natural killer cells, or chimeric antigen receptor T cells.
• Systemic antitumor therapy within 4 weeks before preconditioning, except bridging therapy. For prior nitrosourea or mitomycin chemotherapy, the interval to preconditioning must be at least 6 weeks. For prior small-molecule targeted therapy, the interval must be at least 5 half-lives.
• Systemic corticosteroids at a dose of 10 mg/day or more of prednisone or equivalent, or other immunosuppressive therapy, within 2 weeks before preconditioning, except inhaled, topical, or physiological replacement therapy.
• Major surgery within 4 weeks before screening, or planned major surgery during the study other than the protocol-specified procedure for lymph node collection.
• Other malignancy within 5 years before screening or concurrently, except malignancy treated locally and cured with no antitumor therapy required for at least 1 year, such as non-melanoma skin cancer or cervical carcinoma in situ.
• Active autoimmune disease, a history of autoimmune disease, or a condition requiring systemic corticosteroids or immunosuppressive therapy at more than 10 mg/day of prednisone or equivalent.
• History of organ transplantation or hematopoietic stem cell transplantation.
• Infectious disease within 1 year before screening, including positive human immunodeficiency virus, syphilis, or cytomegalovirus DNA; active pulmonary tuberculosis, or a history of active pulmonary tuberculosis for more than 1 year without adequate treatment; positive hepatitis B surface antigen, or positive hepatitis B core antibody with hepatitis B virus DNA above the lower limit of normal at the study site; positive hepatitis C virus antibody with hepatitis C virus RNA above the lower limit of normal. Inactive carriers may participate if antiviral therapy is arranged as appropriate and nucleic acid levels are monitored periodically during the study.
• Live or attenuated vaccine within 4 weeks before preconditioning.
• Clinically significant cardiovascular disease, including but not limited to:
• Congestive heart failure classified as New York Heart Association class higher than 2.
• Unstable angina.
• Myocardial infarction within the past 3 months.
• Any supraventricular or ventricular arrhythmia requiring treatment or intervention.
• Interstitial pneumonia, clinically significant active pneumonia at screening, or other respiratory disease that significantly affects lung function.
• Refractory or intractable epilepsy, pleural effusion, ascites, or pericardial effusion not controlled by medication, active gastrointestinal bleeding, or any contraindication to interleukin-2.
• History of hypersensitivity to any component of the study drugs, including but not limited to SND002 Cell Injection, cyclophosphamide, fludarabine, interleukin-2, dimethyl sulfoxide (DMSO), human serum albumin, or gentamicin.
• Treatment with another investigational product within 4 weeks before screening, or planned participation in another investigational product study during the study.
• Any other condition the investigator considers unsuitable for participation, for example Grade 3 or higher adverse reactions with prior immunotherapy.