locally advanced head and neck squamous cell carcinoma
Conditions
Interventions
Intervention Group:Immune Checkpoint Inhibitors in Combination With Engineered Mitochondrial Vaccine
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >= 18 years, both genders eligible. 2. Pathologically confirmed head and neck squamous cell carcinoma (HNSCC) meeting the following criteria: a) Clinical stage II-IVB according to the AJCC 8th Edition (nasopharyngeal carcinoma is excluded); b) Positive expression of IMP3 protein; c) Clinically resectable as determined by a Multidisciplinary Team (MDT); d) Subjects must be willing and able to undergo radical surgery. 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1. 4. Adequate organ and bone marrow function, defined as: a) Hematology: Absolute neutrophil count (ANC) >= 1.5 × 10^9/L; Platelet count (PLT) >= 80 × 10^9/L; Hemoglobin (HGB) >= 8 g/dL; b) Liver Function: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphatase (ALP) = 2.8 g/dL; d) Renal Function: Serum creatinine (Cr) 60 mL/min; e) Coagulation: International Normalized Ratio (INR) <= 1.5; Activated Partial Thromboplastin Time (APTT) <= 1.5 × ULN. 5. Subjects must voluntarily participate in the study, sign the Informed Consent Form (ICF), and be able to comply with the scheduled visits and protocol procedures.
Exclusion criteria
Exclusion criteria: 1. History of other malignant tumors within the past 5 years, except for cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical cancer in situ, gastrointestinal intramucosal carcinoma, or other malignancies that the investigator deems eligible. 2. Any active autoimmune disease or history of autoimmune disease, including but not limited to immune-related neurological diseases, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease (Crohn's disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome (except for Type I diabetes mellitus on a stable dose of insulin). 3. Contraindications related to subcutaneous injection (specific to vaccination):a) Active inflammation, trauma, or skin breakdown at the intended injection site;b) Severe bleeding or coagulation tendency, or significantly reduced platelets/clotting factors assessed by the investigator as high risk for bleeding;c) Any abnormal or permanent body art (e.g., tattoos) at the intended injection site that, in the investigator's opinion, would interfere with the observation of local skin reactions. 4. Known allergy to the study drugs or any excipients. History of severe allergies to any drugs, food, or vaccines (e.g., anaphylactic shock, laryngeal edema, dyspnea, Henoch-Schonlein purpura, thrombocytopenic purpura, or Arthus reaction). 5. Prior receipt of any of the following treatments:a) Prior treatment with PD-1, PD-L1, PD-L2, CTLA-4, EGFR antibodies, or EGFR-TKIs;b) Prior vaccination with any anti-tumor vaccines;c) Receipt of any live/active vaccines against infectious diseases (e.g., influenza, varicella) within 4 weeks prior to the first dose or planned during the study period. 6. Requirement for systemic steroid therapy (prednisone equivalent dose > 10 mg/day) within 14 days prior to enrollment. 7. Major surgery or severe trauma within 4 weeks prior to the first dose. 8. Toxicity from prior anti-tumor therapy not recovered to = 10 mmol/L); poorly controlled hypertension (SBP > 150 mmHg and/or DBP > 100 mmHg); LVEF 450 msec (males) or > 470 msec (females); or other ECG abnormalities deemed by the investigator to pose extra risk. 10. History of interstitial lung disease (ILD), non-infectious pneumonitis, or high suspicion of ILD; or any condition that might interfere with the detection or management of drug-related pulmonary toxicity (except for asymptomatic drug-induced or radiation-induced pneumonitis); active tuberculosis (TB) or history of uncontrolled TB. 11. Hyperthyroidism or organic thyroid disease. Hypothyroidism on a stable dose of thyroid replacement therapy or hypothyroidism that can be controlled by replacement therapy (as confirmed by the investigator and/or endocrinology) is eligible. 12. Active infection, unexplained
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability; | — |
Secondary
| Measure | Time frame |
|---|---|
| Surgical feasibility;Survival prognosis;Objective Response Rate;Systemic Immunogenicity Assessment;Pathological Complete Response (pCR) rate;Major Pathological Response (MPR) rate; | — |
Countries
China
Contacts
Public ContactPengXingchen,Weiyuquan
West China Hospital, Sichuan University
Outcome results
None listed