Advanced Solid Tumor
Conditions
Interventions
experimental group:Neo-T infusion
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Before HLA testing and neoantigen testing, it is necessary to verify that the subject meets the criteria marked with * (infectious disease testing is allowed to be performed at the same time as HLA typing) 1. *Aged 18 to 75 years old; 2. *Subjects with pathologically confirmed advanced solid tumors, and has at least one measurable tumor lesion according to RECIST1.1; 3. Subjects carry HLA-A0201, HLA-A1101 or HLA-A2402; 4. Subjects could provide sufficient paraffin-embedded tumor tissues or biopsy tumor tissues (biopsy tumor tissues is recommended) for sequencing, and the quality of sequencing data and predicted neoantigen meet the requirement; 5. Subjects must have received systemic standard treatment before enrollment, and currently have no effective treatment methods, and meet the following requirements: Neoantigen-positive advanced solid tumors (mainly advanced melanoma, esophageal cancer, cholangiocarcinoma and colorectal cancer). Notes: The effective treatment methods referred to the latest version of guidelines for Diagnosis and Treatment of Melanoma, Colorectal Cancer, Esophageal Cancer published by Chinese Society of Clinical Oncology; 6. *Subjects are volunteer to participate in this clinical research; the subjects or their legal guardians should fully understand this research and sign the informed consent; willing to follow and finish all trial procedures; 7. *ECOG score =6 months; 10. Subjects must be willing to practice birth control during the period of study and for up to three months after the end of the treatment, the blood pregnancy test of women of childbearing age is negative; 11. Laboratory tests and the functions of vital organs must meet the following criteria: 1) *Negative for HIV antibody, Treponema pallidum and Hepatitis C virus antibody; Hepatitis B virus DNA test value is lower than the upper limit of normal; 2) Hematology: absolute neutrophils count (ANC) >=1.5x10^9/L, white blood cell count (WBC) >=3x10^9/L, absolute lymphocyte count (LYM) >=0.8x10^9/L, platelet count ( PLT) >=100x10^9/L, hemoglobin (HGB) >=90g/L; 3) Chemistry: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =50%; 12. Subjects must meet the following criteria at the time they receive lymphodepletion regimen: 1) More than four weeks must have elapsed since any prior chemotherapy, small molecule targeted drugs, other clinical trial research drugs, Chinese medicine with anti-tumor indications and other anti-tumor treatments, and patients toxicities must have recovered to a grade 1 or less (except alopecia, vitiligo and other events that considered to be tolerable by the investigator); 2) If patients have undergone surgical treatment within the past 3 weeks, the toxicity must restored to grade 1 or less; 3) More than eight weeks must have elapsed since PD-1 antibody therapy, and more than six must have elapsed since CTLA-4 antibody and other antibody therapies, and the im
Exclusion criteria
Exclusion criteria: Before HLA and Neoantigen testing, it is necessary to verify that the subjects do not meet the exclusion criteria marked with *. 1* Women of child-bearing potential who are pregnant or breastfeeding; 2. *History of severe immediate hypersensitivity reaction to any of the agents used in this study. 3. *History of organ transplantation; 4. Subjects with the unstable central nervous system metastasis, or acute meningitis (except for subjects with treated and clinically treated and clinical stable brain metastases). Clinical stability needs to meet the following criteria at least 4 weeks before apheresis: 1) There was no new brain metastases or progressive brain metastases (confirmed by MRI); 2) Subjects were treated without hormone for at least 2 weeks; 3) There were no new neurological symptoms and the original neurological symptoms had returned to normal. 5. * any patients with active autoimmune diseases or a history of autoimmune diseases considered unsuitable by the investigator, including but not limited to the following diseases: such as systemic lupus erythematosus, immune related neuropathy, multiple sclerosis, Guillain Barre syndrome, myasthenia gravis, connective tissue disease, inflammatory bowel disease including Crohn's disease and ulcerative colitis (except vitiligo, eczema, type I diabetes, rheumatoid arthritis and other joint diseases, Sjogren's syndrome and psoriasis controlled by local drugs); 6. Accompanied by uncontrollable medical diseases or infections, such as acute active infections requiring systemic treatment with antibiotics, antiviral or antifungal agents within the 2 weeks before enrollment; 7. Subjects with severe liver and kidney dysfunction ( uncontrollable liver and kidney disease, the results of chemistry test the criteria of eleventh inclusion criteria ), or uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease, or poorly controlled hypertension (systolic blood pressure >160mmHg and / or diastolic blood pressure >90mmHg), or clinically significant (e.g. active) cardiovascular and cerebrovascular diseases, such as cerebrovascular accident (within 6 months before signing the informed consent), myocardial infarction (within 6 months before signing the informed consent), unstable angina pectoris, congestive heart failure with NYHA grade II or above, severe arrhythmia that cannot be controlled by drugs, the results of ECG in three consecutive times (at least 5 minutes interval each time) show clinically significant abnormalities, or mental illness and drug abusers, any situation that may increase the risk of the subjects or interfere with the test results considered by investigator; 8. Subjects who plan to receive Glucocorticoid (prednisone or equivalent dose > 10mg / day) or other immunosuppressive agents within 4 weeks before lymphodepletion and during the study period. Note: when there is no active autoimmune disease, prednisone or instead adrenal drugs substitute with the same dosage <=10mg / day are allowed to be used; Subjects were allowed to use local, ocular, intra-articular, intranasal and inhaled corticosteroids (extremely low degree of systemic absorption); 9. Subjects plan to receive immunomodulatory drugs (such as interferon, GM-CSF, thymosin, gamma globulin, interleukin, etc.) within 4 weeks before lymphodepletion and during the study period due to certain conditions; 10. * Subjects were unable or unwilling to comply with the requirements of the st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events (AE);Dose limited toxicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate;Progression-free survival;Duration of response;Disease control rate;Overall survival; | — |
Countries
China
Contacts
Public ContactRuihua Shi
Sun Yat-Sen University Cancer Center
Outcome results
None listed