Neoadjuvant ICI and Mitochondrial Vaccine for Resectable HNSCC

Korábbi kezelés

• Requirement for systemic steroid therapy (prednisone equivalent dose > 10 mg/day) within 14 days prior to enrollment.
• Major surgery or severe trauma within 4 weeks prior to the first dose.
• Toxicity from prior anti-tumor therapy not recovered to ≤ CTCAE (Version 5.0) Grade 1 (except for alopecia, or sequelae of neurotoxicity related to prior platinum therapy) or levels specified in the inclusion/exclusion criteria.
• Active infection, unexplained fever occurring within 48 hours prior to the first dose, or use of systemic antibiotics within 1 week prior to signing the Informed Consent Form (ICF).
• Receipt of any other investigational drug within 4 weeks prior to the first dose, or concurrent enrollment in another clinical study, except for observational (non-interventional) studies or the follow-up phase of an interventional study.

Más betegség

• 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.
• 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).
• 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).
• 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.
• 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.
• Active Hepatitis B (HBV DNA ≥ 2000 IU/mL or 10\^4 copies/mL), Hepatitis C (HCV antibody positive and HCV RNA above the limit of detection), or known history of HIV infection or AIDS.
• History of neurological or psychiatric disorders, such as epilepsy or dementia.
• History of drug abuse or alcohol abuse within the past 3 months.

Laborértékek

• Contraindications related to subcutaneous injection (specific to vaccination):
  • Active inflammation, trauma, or skin breakdown at the intended injection site;
  • Severe bleeding or coagulation tendency, or significantly reduced platelets/clotting factors assessed by the investigator as high risk for bleeding;
  • 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.
• Prior receipt of any of the following treatments:
  • Prior treatment with PD-1, PD-L1, PD-L2, CTLA-4, EGFR antibodies, or EGFR-TKIs;
  • Prior vaccination with any anti-tumor vaccines;
  • 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.
• Severe medical conditions, including: Grade II or higher cardiac dysfunction (NYHA criteria); ischemic heart disease (e.g., myocardial infarction or angina); clinically significant supraventricular or ventricular arrhythmias; poorly controlled diabetes (fasting blood glucose ≥ 10 mmol/L); poorly controlled hypertension (SBP > 150 mmHg and/or DBP > 100 mmHg); LVEF < 50% on echocardiography; QTc interval > 450 msec (males) or > 470 msec (females); or other ECG abnormalities deemed by the investigator to pose extra risk.

Egyéb

• Pregnant or lactating women; subjects (or their partners) planning for pregnancy or engaging in unprotected sexual intercourse from screening until 3 months after the end of the study.
• Other factors judged by the investigator that may interfere with the completion of the study treatment or follow-up.

• Aged ≥ 18 years, both genders eligible.
• Pathologically confirmed head and neck squamous cell carcinoma (HNSCC) meeting the following criteria:
  • Clinical stage II-IVB according to the AJCC 8th Edition (nasopharyngeal carcinoma is excluded);
  • Positive expression of IMP3 protein;
  • Clinically resectable as determined by a Multidisciplinary Team (MDT);
  • Subjects must be willing and able to undergo radical surgery.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• Adequate organ and bone marrow function, defined as:
  • Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelet count (PLT) ≥ 80 × 10\^9/L; Hemoglobin (HGB) ≥ 8 g/dL;
  • Liver Function: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphatase (ALP) ≤ 2.5 × Upper Limit of Normal (ULN); Total bilirubin (TBIL) ≤ 1.5 × ULN;
  • Albumin (ALB) ≥ 2.8 g/dL;
  • Renal Function: Serum creatinine (Cr) ≤ 1.5 × ULN or Creatinine Clearance (CCR) > 60 mL/min;
  • Coagulation: International Normalized Ratio (INR) ≤ 1.5; Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
• 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.