Solid tumor
Conditions
Interventions
Group A: Patients with advanced/recurrent or stage II/III locally advanced solid tumors that are not suitable for surgery:personalized mRNA neoantigen vaccine(AFN18)
Group B: Radical resection (R0):personalized mRNA neoantigen vaccine(AFN18)
Sponsors
The First Affiliated Hospital of Bengbu Medical College
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1: The age should be between 18 and 75 (inclusive), with no gender restriction. 2: Meeting one of the following conditions: A) Patients with advanced/recurrent or locally advanced solid tumors at stage II/III who are not suitable for surgery, confirmed by histopathological or cytological examination, and have failed or cannot tolerate standard treatments, or have no standard treatment options available. B) Patients who have undergone radical resection (R0) and provided preoperative and postoperative imaging data evidence, with no local recurrence or distant metastasis. Disease-free status must be confirmed before enrollment through whole chest/abdomen/pelvis computed tomography (CT) and/or magnetic resonance imaging (MRI), neck CT and/or MRI, and a complete clinical examination. Head CT is applicable to any patients with MRI contraindications. Postoperative ctDNA is positive. 3: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 4: Subjects meeting criterion 2.A must have at least one measurable target lesion according to RECIST 1.1 criteria. 5: Sufficient tumor and blood samples for NGS gene sequencing (WES and RNAseq) can be obtained through debulking surgery, biopsy, or radical surgery. FFPE (formalin-fixed, paraffin-embedded) tumor samples and biopsy specimens within 1 year. The number of neoantigens identified must be no less than 5. 6: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. 7: Expected survival time of =6 months. 8: No severe hematological, liver, kidney, coagulation, or cardiac dysfunction. Laboratory test results during the screening period (within 14 days before the test date and without prior granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), red blood cell transfusion, or platelet transfusion support therapy) must meet the following criteria: [Note: This sentence is repeated, but the corrected standard to be met is implied.] Laboratory test results for screening (taken within 14 days before the examination date and without prior use of G-CSF, GM-CSF, red blood cell transfusions, or platelet transfusions) must comply with the established standards for the absence of severe hematological, liver, kidney, coagulation, or cardiac dysfunction. Hematology: Absolute Neutrophil Count (ANC) =1.5×10^9/L; Platelets (PLT) =75×10^9/L; Hemoglobin (Hb) =90 g/L Liver Function: Total Bilirubin (TBIL) =1.5×Upper Limit of Normal (ULN) (Except for Gilbert's Syndrome, with liver metastasis =3×ULN); Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) =2.5×ULN (With liver metastasis =5×ULN) Renal Function: Serum Creatinine (Scr) =1.5×ULN; Creatinine Clearance Rate (Ccr) (Only needed when Serum Creatinine >1.5×ULN) =60 mL/min (Calculated using the Cockcroft-Gault formula, see Appendix 5) Coagulation Function: Prothrombin Time (PT) =1.5×ULN; Activated Partial Thromboplastin Time (APTT) =1.5×ULN 9: Male participants and females of childbearing potential must agree to use effective contraception from the time of signing the informed consent form until 3 months after the last dose of medication. For female participants of childbearing potential, a negative blood or urine pregnancy test must be obtained within 7 days prior to the first dose. Definition of females of childbearing potential: Females who have undergone menarche but have not reached menopause (defined as the absence of menstruation for =12
Exclusion criteria
Exclusion criteria: Exclusion criteria: 1: Received anti-tumor treatments such as chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, etc., within 2 weeks or 4 half-lives (whichever is shorter) prior to the first use of the investigational drug, with the following exceptions: Nitrosoureas or mitomycin C within 6 weeks prior to the first use of the investigational drug; Oral fluoropyrimidines and small molecule targeted drugs within 2 weeks or 5 half-lives (whichever is shorter) prior to the first use of the investigational drug; Traditional Chinese medicines with anti-tumor indications within 2 weeks prior to the first use of the investigational drug. 2: Received other unapproved investigational drugs or treatments within 4 weeks prior to the first dose. 3: Received any live vaccine within 4 weeks prior to the first dose. 4: Undergone major organ surgery (excluding biopsy) or suffered significant trauma within 4 weeks prior to the first dose, or required elective surgery during the study period. 5: Received prior cellular therapy (e.g., TCR-T, CAR-T, TIL, tumor vaccines). 6: Patients with microsatellite instability-high (MSI-H) colorectal cancer. 7: Received allogeneic hematopoietic stem cell or bone marrow transplantation, solid organ transplantation, or are currently using immunosuppressive drugs or anti-rejection drugs. 8: Have any active autoimmune disease, history of autoimmune disease, or a history of diseases or syndromes requiring systemic steroid or immunosuppressive drug treatment (except for skin diseases not requiring systemic treatment or childhood asthma/allergies that have resolved and do not require any intervention in adulthood; subjects with a history of autoimmune-mediated hypothyroidism treated with stable doses of thyroxine replacement therapy may be eligible). 9: Used systemic immunosuppressive drugs within 2 weeks prior to the first dose (including but not limited to prednisone > 10 mg/day, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNF-a antagonists). Patients who have received a single, low-dose, systemic immunosuppressive drug (e.g., a single dose of dexamethasone for nausea) may participate in the study after discussion and approval by the investigator. Inhaled corticosteroids (e.g., fluticasone for chronic obstructive pulmonary disease) are allowed. Oral mineralocorticoids (e.g., fludrocortisone for orthostatic hypotension) are allowed. Physiological doses of corticosteroids for adrenal insufficiency are allowed. Subjects with a known allergy to intravenous contrast agents requiring corticosteroid pretreatment will be excluded (corticosteroids have immunosuppressive effects that may interfere with the tolerability and efficacy of AFN18. Given that the study includes imaging studies required after vaccination, subjects requiring corticosteroid pretreatment before intravenous contrast agent administration will be excluded). 10: Have allergies to any active or inactive ingredient of the investigational drug. 11: Adverse reactions from prior anti-tumor treatments have not resolved to CTCAE 5.0 grade = 1 (except for toxicities judged by the investigator to pose no safety risk, such as alopecia, grade 2 peripheral neuropathy, stable hypothyroidism with hormone replacement therapy, etc.). 12: Active hepatitis B (HBsAg positive and HBV-DNA > lower limit of detection at the study center); hepatitis C virus infection (HCV-RNA > lower limit of detection at the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The occurrence and incidence rate of Serious Adverse Events (SAE) and Adverse Events (AE) ; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective response rate (ORR);Immunogenicity Analysis;disease control rate (DCR);duration of response (DOR);disease-free/progression-free survival (DFS/PFS);pathological complete response (pCR) ; | — |
Countries
China
Contacts
Public ContactJin Gongsheng and Zhouhuan
The First Affiliated Hospital of Bengbu Medical College
Outcome results
None listed