colorectal cancer
Conditions
Interventions
900 µg dose group:Muscle injection of individualized tumor neoantigen mRNA vaccine for targeted immunotherapy targeting the specific neoantigens present in the patient'
1200 µg dose group:Muscle injection of individualized tumor neoantigen mRNA vaccine for targeted immunotherapy targeting the specific neoantigens present in the patient'
Sponsors
Hefei Cancer Hospital,Chinese Academy of Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. The age of the subjects should be between 18 and 75 years old (inclusive of both boundaries), and there is no restriction on gender. 2. Patients with digestive tract tumors that meet one of the following conditions: A. Diagnosed by histopathology or cytology, have failed standard treatment or have no standard treatment, are difficult to treat with recurrence, or are locally advanced in stage III. B. Patients with stage II/III operable rectal cancer and high risk of recurrence were included as a subgroup in the study. High risk of recurrence is defined as meeting at least one of the following criteria: a) T4 staging, b) histological grading as poorly differentiated or undifferentiated, c) clinical presentation as intestinal obstruction or perforation, d) histological signs of vascular, lymphatic, and nerve invasion, e) less than 12 lymph nodes cleared around cancer tissue; And the patient tested positive for ctDNA before adjuvant chemotherapy after surgery. If there is pathological confirmation of abdominal implantation lesions through open or laparoscopic surgical exploration, ascites cytology, etc., regardless of whether ctDNA is positive, they can be included in the group. 3. The ECOG score for physical fitness status is 0 or 1. According to RECIST 1.1 criteria, subjects who meet 2. A must have at least one measurable target lesion. 5. Sufficient tumor and blood samples for NGS gene sequencing (WES and RNAseq) can be obtained through tumor reduction surgery, biopsy, or radical surgery. Tumor samples and biopsy specimens fixed in formalin and embedded in paraffin (FFPE) within one year can also be used for this study. The number of newly screened antigens must not be less than 5 in order to meet the basic conditions for inclusion in the group. 6. Expected survival time = 6 months. 7. There should be no serious hematological, liver, kidney, coagulation, or cardiac dysfunction. Laboratory tests during the screening period (no granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), red blood cell transfusion, or platelet transfusion support therapy received within 14 days prior to the examination date) should meet the following criteria: Hematology: Absolute neutrophil count (ANC) >= 1.5 × 10 ^ 9/L; Platelet count (PLT) >= 75 × 10 ^ 9/L; Hemoglobin (Hb) >= 90 g/L Liver function: Total bilirubin (TBIL) = 60 mL/min (calculated according to the Cockcroft Gault formula) Coagulation function: Prothrombin time (PT) = 12 months other than menopause) and
Exclusion criteria
Exclusion criteria: 1.Within 23 weeks prior to the first use of the study drug or within 4 half-lives (whichever is shorter), patients have received anti-tumor treatments such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, or immunotherapy. Exclusions include the following: ? For nitrogen mustard or mitomycin C, it is within 6 weeks prior to the first use of the study drug; ? For oral fluorouracil and small molecule targeted drugs, it is within 2 weeks prior to the first use of the study drug or within 5 half-lives of the drug (whichever is shorter); For traditional Chinese medicine with anti-tumor indications, it is within 2 weeks prior to the first use of the study drug. 2.Within 4 weeks prior to the first administration, had received any other unapproved clinical research drugs or treatments. 3.Within 4 weeks prior to the first administration, any live vaccine has been administered. 4.Within 4 weeks prior to the first administration, the subject has undergone major surgical procedures on major organs (excluding biopsy procedures) or has suffered significant trauma, or requires elective surgery during the trial period. 5.Those who have previously received cell therapy (such as TCR-T, CAR-T, TIL, tumor vaccines). 6.Has previously received allogeneic hematopoietic stem cell or allogeneic bone marrow transplantation, or has previously undergone solid organ transplantation, or is currently using immunosuppressive drugs or anti-transplant rejection drugs. 7.Any active autoimmune disease, history of autoimmune disease, or history of a disease or syndrome requiring systemic steroid hormones or immunosuppressive drugs for treatment (excluding dermatological conditions requiring systemic treatment or childhood asthma/allergy that has been cured and does not require any intervention in adulthood; subjects with a history of autoimmune-mediated hypothyroidism and stable dose of thyroid hormone replacement therapy can be included in this study). 8.For the first administration, use systemic immunosuppressive drugs within 2 weeks prior to the administration (including but not limited to prednisone > 10 mg/day, cyclophosphamide, azathioprine, methotrexate, thalidomide, thalidomide, and TNF-a antagonists). Patients who have received a single, low-dose, systemic immunosuppressive drug (for example, a single dose of dexamethasone for treating nausea) can participate in the study after discussing with the PI and obtaining approval. Inhalation corticosteroids (such as fluticasone for treating chronic obstructive pulmonary disease) are allowed. Oral mineralocorticoids (such as fludrocortisone for patients with orthostatic hypotension) are allowed. Physiological doses of corticosteroids for treating adrenal insufficiency are permitted. Subjects with a history of autoimmune-mediated hypothyroidism can be enrolled in this study. 9.Those who are allergic to any active or inactive ingredients of the research drug. 10.The adverse reactions from previous anti-tumor treatments have not yet recovered to a CTCAE 5.0 grade evaluation of <= 1 (except for toxicities that the investigator deems to be safe, such as hair loss, grade 2 peripheral neuropathy, stable hypothyroidism after hormone replacement therapy, etc.). 11.Active hepatitis B (with HBsAg positive and HBV-DNA above the detection limit set by the research center); hepatitis C virus infection (HCV-RNA above the detection limit set by the research center); positive HIV antibody test result; positive Trepone
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| vital signs;coagulation function;12-lead electrocardiogram;blood biochemistry;ECOG score;blood routine examination;urine routines;thyroid function;physical examination; | — |
Secondary
| Measure | Time frame |
|---|---|
| Tumor imaging assessment; | — |
Countries
China
Contacts
Public ContactJinman fang
Hefei Cancer Hospital,Chinese Academy of Sciences
Outcome results
None listed