Neoadjuvant ICI and Mitochondrial Vaccine for Resectable HNSCC

NCT07572864 | Not Yet Recruiting Phase 2

• 1 other identifier: 2026(876)
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response

  Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells.

  At the time of surgery (approximately 6 weeks after enrollment).

Secondary Outcomes (3)

• 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).

• Pathologic Complete Response

  At the time of surgery (approximately 6 weeks after enrollment).

• Objective Response Rate

  From the start of neoadjuvant therapy to the end of neoadjuvant therapy, the duration is approximately 2 months

Study Arms (1)

IMP3-Mito Vaccine plus ICI Combination Group

EXPERIMENTAL

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); Drug: Immune checkpoint inhibitor (ICI)

Interventions

Engineered Mitochondrial Vaccine (IMP3-Mito) BIOLOGICAL

A vaccine targeting the IMP3 antigen, utilizing an engineered mitochondrial platform. Administered via subcutaneous injection.

IMP3-Mito Vaccine plus ICI Combination Group

Immune checkpoint inhibitor (ICI) DRUG

PD-1 inhibitor administered via intravenous infusion to synergistic with the mitochondrial vaccine.

IMP3-Mito Vaccine plus ICI Combination Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.
• 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).
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (6)

• Gulley JL, Borre M, Vogelzang NJ, Ng S, Agarwal N, Parker CC, Pook DW, Rathenborg P, Flaig TW, Carles J, Saad F, Shore ND, Chen L, Heery CR, Gerritsen WR, Priou F, Langkilde NC, Novikov A, Kantoff PW. Phase III Trial of PROSTVAC in Asymptomatic or Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2019 May 1;37(13):1051-1061. doi: 10.1200/JCO.18.02031. Epub 2019 Feb 28.

  PMID: 30817251 BACKGROUND

• Fan L, Wu D, Goremykin V, Xiao J, Xu Y, Garg S, Zhang C, Martin WF, Zhu R. Phylogenetic analyses with systematic taxon sampling show that mitochondria branch within Alphaproteobacteria. Nat Ecol Evol. 2020 Sep;4(9):1213-1219. doi: 10.1038/s41559-020-1239-x. Epub 2020 Jul 13.

  PMID: 32661403 BACKGROUND

• Pierini S, Fang C, Rafail S, Facciponte JG, Huang J, De Sanctis F, Morgan MA, Uribe-Herranz M, Tanyi JL, Facciabene A. A Tumor Mitochondria Vaccine Protects against Experimental Renal Cell Carcinoma. J Immunol. 2015 Oct 15;195(8):4020-7. doi: 10.4049/jimmunol.1500281. Epub 2015 Sep 16.

  PMID: 26378078 BACKGROUND

• Tse SW, McKinney K, Walker W, Nguyen M, Iacovelli J, Small C, Hopson K, Zaks T, Huang E. mRNA-encoded, constitutively active STINGV155M is a potent genetic adjuvant of antigen-specific CD8+ T cell response. Mol Ther. 2021 Jul 7;29(7):2227-2238. doi: 10.1016/j.ymthe.2021.03.002. Epub 2021 Mar 5.

  PMID: 33677092 BACKGROUND

• Fang C, Mo F, Liu L, Du J, Luo M, Men K, Na F, Wang W, Yang H, Wei X. Oxidized mitochondrial DNA sensing by STING signaling promotes the antitumor effect of an irradiated immunogenic cancer cell vaccine. Cell Mol Immunol. 2021 Sep;18(9):2211-2223. doi: 10.1038/s41423-020-0456-1. Epub 2020 May 12.

  PMID: 32398808 BACKGROUND

• Luo J, Mo F, Zhang Z, Hong W, Lan T, Cheng Y, Fang C, Bi Z, Qin F, Yang J, Zhang Z, Li X, Que H, Wang J, Chen S, Wu Y, Yang L, Li J, Wang W, Chen C, Wei X. Engineered mitochondria exert potent antitumor immunity as a cancer vaccine platform. Cell Mol Immunol. 2024 Nov;21(11):1251-1265. doi: 10.1038/s41423-024-01203-4. Epub 2024 Aug 20.

  PMID: 39164536 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Xingchen Peng, Professor

CONTACT

+8618980606753; pxx2014@163.com

Yiyan Pei, Doctor

CONTACT

dr.peiyy@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Professor

Study Record Dates

• First Submitted: April 24, 2026
• First Posted: May 7, 2026
• Study Start: April 28, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: May 7, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)