Head and Neck Squamous Cell Carcinoma
Conditions
Brief summary
Head and neck squamous cell carcinoma (HNSCC) presents a significant clinical challenge, as over 60% of patients are diagnosed at a locally advanced stage with a high risk of recurrence. Although the landmark KEYNOTE-689 trial established neoadjuvant immune checkpoint inhibitor (ICI) therapy as a new standard of care, the pathological complete response (pCR) rate remains unsatisfactory at only 3.0%, highlighting an urgent need for optimized combination strategies. This prospective, single-arm, single-center clinical study aims to evaluate the safety, tolerability, and preliminary efficacy of a novel neoadjuvant and adjuvant regimen combining an engineered mitochondrial vaccine (IMP3-Mito) with ICIs for patients with resectable, IMP3-positive locally advanced HNSCC. The rationale is based on a "Prime-and-Release" synergistic mechanism: the engineered mitochondrial vaccine serves as a potent "natural adjuvant" to activate dendritic cells and prime tumor-specific T-cell responses against the IMP3 antigen, while the ICI subsequently releases the immune brakes within the tumor microenvironment. By integrating these two modalities, the study seeks to achieve deeper pathological responses and improve long-term survival, while simultaneously providing clinical evidence for the transformative potential of the mitochondrial engineering platform in overcoming the limitations of conventional tumor vaccines.
Interventions
BIOLOGICALEngineered Mitochondrial Vaccine (IMP3-Mito)
A vaccine targeting the IMP3 antigen, utilizing an engineered mitochondrial platform. Administered via subcutaneous injection.
PD-1 inhibitor administered via intravenous infusion to synergistic with the mitochondrial vaccine.
Sponsors
West China Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged ≥ 18 years, both genders eligible. 2. Pathologically confirmed head and neck squamous cell carcinoma (HNSCC) meeting the following criteria: 1. Clinical stage II-IVB according to the AJCC 8th Edition (nasopharyngeal carcinoma is excluded); 2. Positive expression of IMP3 protein; 3. Clinically resectable as determined by a Multidisciplinary Team (MDT); 4. 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: 1. Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelet count (PLT) ≥ 80 × 10\^9/L; Hemoglobin (HGB) ≥ 8 g/dL; 2. 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; 3. Albumin (ALB) ≥ 2.8 g/dL; 4. Renal Function: Serum creatinine (Cr) ≤ 1.5 × ULN or Creatinine Clearance (CCR) \> 60 mL/min; 5. 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
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): 1. Active inflammation, trauma, or skin breakdown at the intended injection site; 2. Severe bleeding or coagulation tendency, or significantly reduced platelets/clotting factors assessed by the investigator as high risk for bleeding; 3. 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: 1. Prior treatment with PD-1, PD-L1, PD-L2, CTLA-4, EGFR antibodies, or EGFR-TKIs; 2. Prior vaccination with any anti-tumor vaccines; 3. 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 ≤ CTCAE (Version 5.0) Grade 1 (except for alopecia, or sequelae of neurotoxicity related to prior platinum therapy) or levels specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response | At the time of surgery (approximately 6 weeks after enrollment). | Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | From the first dose until the completion of the 12-month post-operative follow-up (approximately 14 months in total). | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of the product was also an AE. The number of participants who experienced an AE was reported for each arm. |
| Pathologic Complete Response | At the time of surgery (approximately 6 weeks after enrollment). | Pathologic Complete Response (pCR) was defined as the absence of viable tumor cells. |
| Objective Response Rate | From the start of neoadjuvant therapy to the end of neoadjuvant therapy, the duration is approximately 2 months | Objective Response Rate (ORR) was defined as the percentage of participants with a best overall response of CR or PR using RECIST Criteria. |
Countries
China
Contacts
CONTACTXingchen Peng, Professor
CONTACTYiyan Pei, Doctor
Outcome results
None listed