HPV16/18-positive unresectable recurrent or metastatic solid tumors
Conditions
Interventions
treatment group:reRNA-HPV tumor vaccine/PD-1 toripalimab injection
Sponsors
The First Affiliated Hospital of Nanyang Medical College
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Male or female, aged 18-75 years old; 2. Histologically or cytologically confirmed HPV16/18-positive unresectable recurrent or metastatic solid tumors (including but not limited to anal cancer, cervical and head and neck cancer): failure of standard treatment (disease progression after treatment or failure of treatment) Tolerance) and there is no effective treatment, or there is no standard treatment plan, or standard treatment cannot be obtained due to objective conditions; 3. Eastern Cooperative Oncology Group (ECOG) physical status (PS) score is 0-2; 4. Expected survival period >= 3 months; 5. At least 1 measurable lesion according to RECIST 1.1 criteria; Note: Lesions located in previously irradiated areas can only be evaluated for measurable lesions if there is objective evidence that the lesions have progressed before the study is enrolled; 6. The following laboratory tests have been carried out within 14 days before the signing of the informed consent, and the test results show that the organ function and bone marrow reserve are good: (1) Bone marrow function: absolute neutrophil count (ANC) >= 1.5 x 10^9/L; platelet count (PLT) >= 75 x 10^9/L; hemoglobin content (HGB) >= 90 g/L. No use of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), red blood cell transfusion and platelet transfusion within 14 days before the examination; (2) Liver function: serum total bilirubin (TBIL) = 30 mL/min, whether measured actually by collecting urine or estimated using the Cockcroft-Gault formula; (4) Coagulation function: prothrombin time (PT), international normalized ratio (INR) and partial thromboplastin time (PTT) <= 1.5 x ULN. If the subject is receiving anticoagulant therapy, as long as the PT is within the prescribed range of the anticoagulant drug; 7. Patients suffering from immune-mediated endocrine diseases after receiving immune checkpoint inhibitor therapy and requiring hormone replacement therapy can be included in the study. Patients requiring prednisone-containing hormone replacement therapy were eligible for study enrollment if the daily dose did not exceed 10 mg; 8. Eligible patients (male and female) of childbearing potential must agree to be at least Within 6 months) use reliable contraceptive methods (hormone or barrier method or abstinence); female patients of childbearing age must have a negative blood pregnancy test within 7 days before enrollment; 9. The patient fully understands the purpose, nature, method and possible adverse reactions of the trial, volunteers as a participant, and signs an informed consent form (ICF) before any procedure begins.
Exclusion criteria
Exclusion criteria: 1. Received radiotherapy, chemotherapy, biological therapy, endocrine therapy, immunotherapy and other anti-tumor treatments (including experimental treatments) within 4 weeks before the first administration; 2. Received a live virus vaccine within 4 weeks prior to the first dose; 3. Has undergone major surgery within 2 weeks; for major surgery performed more than 2 weeks ago, all surgical wounds must be healed and have no signs of infection or dehiscence; 4. Systemic treatment with glucocorticoids (daily dose > 10 mg of prednisone or equivalent doses) or other immunosuppressive drugs within 14 days before the first administration; Note: Inhaled, intranasal, intraarticular, or topical (including intraocular) steroids are permitted. Steroid replacement therapy was permitted in patients with adrenal insufficiency, and fludrocortisone was permitted as mineralocorticoid replacement therapy; 5. Patients who have undergone splenectomy; 6. Patients with known or screening findings of active CNS metastases and/or cancerous meningitis. However, the following subjects are allowed to enroll: (1) Patients with asymptomatic brain metastases (that is, no progressive central nervous system symptoms caused by brain metastases, and do not need to use corticosteroids) can participate; (2) Subjects with treated and stable brain metastases for at least 2 months, without evidence of new or enlarged brain metastases. Patients with cancerous meningitis were excluded from the study regardless of their clinical status; 7. Except for hearing loss, hair loss and fatigue, the adverse reactions of previous anti-tumor therapy have not recovered to NCI CTCAE v5.0 grade evaluation <= grade 1; 8. Any grade 4 immune-related AE (irAE) occurred when receiving immunotherapy in the past (patients with endocrine diseases receiving replacement therapy or with asymptomatic serum amylase or lipase elevation can be included in the study), Any irAE leading to permanent discontinuation of treatment, or any Grade 3 irAE occurred within <= 6 months prior to the first dose; Note: This article is only for the combined treatment group subjects; 9. Received non-glucocorticoid immunosuppressants within 1 month before the first dose; 10. Suffering from active autoimmune disease or inflammatory disease (including inflammatory bowel disease [such as ulcerative colitis or Crohn's disease], diverticulitis [except diverticular disease], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome or Wegener's syndrome [granulomatous polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.) or a history of the disease within 2 years (systematic Subjects with treated vitiligo, psoriasis, alopecia, or Graves' disease, hypothyroidism requiring only thyroid hormone replacement therapy, and type 1 diabetes requiring only insulin replacement therapy can be enrolled). Known history of primary immunodeficiency. Only patients with autoimmune antibody positive will confirm whether there is an autoimmune disease according to the investigator's judgment; 11. Interstitial lung disease (requiring steroid use), idiopathic pulmonary fibrosis, pneumonia (including drug-induced pneumonia) or organizing pneumonia (eg, bronchiolitis obliterans, cryptogenic organizing pneumonia) medical history; Note: Asymptomatic pneumonia patients who do not require steroid therapy for lung inflammation can be enrolled in the study; 12. Cardiovascular and cerebrovascular diseases meet any of the fol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse event; | — |
Secondary
| Measure | Time frame |
|---|---|
| T lymphocyte responses;lymphocyte subsets;Changes in serum cytokines compared to baseline;disease response rate;overall response rate;Progression Free Survival;Overall Survival; | — |
Countries
China
Contacts
Public ContactShi Pei
The First Affiliated Hospital of Nanyang Medical College
Outcome results
None listed