Neoadjuvant ICI and Mitochondrial Vaccine for Resectable HNSCC

May 6, 2026 updated by: Xingchen Peng, West China Hospital

Efficacy and Safety of Immune Checkpoint Inhibitors in Combination With Engineered Mitochondrial Vaccine as Neoadjuvant and Adjuvant Therapy for Resectable Head and Neck Squamous Cell Carcinoma: A Single-Arm, Single-Center Clinical Study.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

9

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Xingchen Peng, Professor
  • Phone Number: +8618980606753
  • Email: pxx2014@163.com

Study Contact Backup

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • West China Hospital, Sichuan University
        • Contact:
          • Xingchen Peng, Professor
          • Phone Number: 18980606753
          • Email: pxx2014@163.com
      • Chengdu, Sichuan, China, 610041
        • Not yet recruiting
        • West China Hospital, Sichuan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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/exclusion criteria.
  9. 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.
  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 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).
  13. 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.
  14. History of neurological or psychiatric disorders, such as epilepsy or dementia.
  15. History of drug abuse or alcohol abuse within the past 3 months.
  16. 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.
  17. 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.
  18. Other factors judged by the investigator that may interfere with the completion of the study treatment or follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IMP3-Mito Vaccine plus ICI Combination Group
Participants with resectable IMP3-positive LA-HNSCC will receive neoadjuvant engineered mitochondrial vaccine (IMP3-Mito) in combination with immune checkpoint inhibitors, followed by surgery and subsequent adjuvant combination therapy.
Biological: Engineered Mitochondrial Vaccine (IMP3-Mito)
A vaccine targeting the IMP3 antigen, utilizing an engineered mitochondrial platform. Administered via subcutaneous injection.
Drug: Immune checkpoint inhibitor (ICI)
PD-1 inhibitor administered via intravenous infusion to synergistic with the mitochondrial vaccine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathologic Response
Time Frame: At the time of surgery (approximately 6 weeks after enrollment).
Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells.
At the time of surgery (approximately 6 weeks after enrollment).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experienced an Adverse Event (AE)
Time Frame: 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.
From the first dose until the completion of the 12-month post-operative follow-up (approximately 14 months in total).
Pathologic Complete Response
Time Frame: At the time of surgery (approximately 6 weeks after enrollment).
Pathologic Complete Response (pCR) was defined as the absence of viable tumor cells.
At the time of surgery (approximately 6 weeks after enrollment).
Objective Response Rate
Time Frame: 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.
From the start of neoadjuvant therapy to the end of neoadjuvant therapy, the duration is approximately 2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 28, 2026

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

April 24, 2026

First Submitted That Met QC Criteria

April 30, 2026

First Posted (Actual)

May 7, 2026

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026(876)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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