Immunotherapy in Subjects With HPV-6 Associated Aerodigestive Precancerous Lesions and Malignancies

Study Overview
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Brief Summary
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This is a Phase I, open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3106 alone or in combination with INO-9012 DNA vaccines delivered by Electroporation to subjects with HPV6 associated aerodigestive precancerous lesions and malignancies.

Detailed Description
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This is a Phase I, open-label, study to evaluate the safety, tolerability, and immunogenicity of 3 mg or 6 mg INO-3106 alone or in combination with 1 mg of INO-9012 (DNA plasmid encoding human interleukin 12) delivered by electroporation (EP) in subjects with HPV6 associated aerodigestive precancerous lesions and malignancies. Subjects will be enrolled in 2 cohorts (3 subjects in each cohort): Cohort I: First 3 subjects will be enrolled sequentially and will receive INO-3106 alone or in combination with INO-9012. Cohort II: The next 3 subjects will be treated with 6 mg of INO-3106 and 1 mg of INO-9012, or at the MTD (Maximum Tolerated Dose) determined in Cohort I.

Official Title
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A Study of HPV Specific Immunotherapy in Subjects With HPV6 Associated Aerodigestive Precancerous Lesions and Malignancies

Conditions
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Aerodigestive Precancerous Lesions and Malignancies

Intervention / Treatment
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* Biological: INO-3106, INO-9012


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated written Ethics Committee approved informed consent Age ≥18 years Histologically documented HPV-6 positive aerodigestive invasive malignancy (mucosal squamous cell head and neck cancer or lung cancer) who have completed therapies such as radiation/chemoradiation/chemotherapy; or Histologically documented HPV-6 positive papilloma or HPV-6 related premalignant lesion (i.e., carcinoma in situ) in aerodigestive or head and neck regions. Prior to study entry, subjects will have exhausted all treatments that are/have been used in these indications which may include any combination of surgery, anti-viral therapy, chemotherapy and/or radiation therapy. Core biopsy must be obtained prior to enrollment to confirm invasive cancer. Archival material is allowed. Adequate bone marrow, hepatic, and renal function. ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 cells/mm3, hemoglobin ≥ 9.0 g/dL, concentrations of total serum bilirubin within 1.5 x upper limit of normal (ULN), AST, ALT within 2.5x ULN, CPK within 2.5 x ULN, serum creatinine ≤ 1.5x ULN ECOG (Eastern Cooperative Oncology Group) performance status of 0-2 Exclusion Criteria: Participation in a clinical trial within 30 days before entry Any cardiac pre-excitation syndromes, e.g. Wolff-Parkinson-White syndrome Presence of metal implants within 5 cm of the planned site(s) of injection Anticipated concomitant immunosuppressive therapy (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids) Administration of any vaccine within 6 weeks of enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort I<br>3 mg of INO-3106 (D0); 6 mg of INO-3106 (Wk3); 6 mg of INO-3106 + 1 mg of INO-9012 (Wk6); 6 mg of INO-3106 + 1 mg of INO-9012 (Wk9); | Biological: INO-3106, INO-9012<br> <br> |
| Experimental: Cohort II<br>6 mg of INO-3106 in combination with 1 mg of INO-9012, or at the MTD determined above at D0, Wk3, Wk6, Wk9 | Biological: INO-3106, INO-9012<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events measured and graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE), NCI version 4.03 |  | Up to 6 months | 
| Injection site reactions including skin erythema, induration pain and tenderness at administration site |  | Up to 15 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HPV6 specific Ig levels |  | Up to 6 months | 
| Number of antigen-specific IFN-γ-secreting cells in response to stimulation with HPV6 by antigen-specific IFN-γ ELISpot assays |  | Up to 6 months | 
| Cytotoxic T cells in response to HPV6 specific immunotherapy by flow cytometry |  | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aerodigestive Lesions and Malignancies, Human Papillomavirus, Squamous Cell Carcinoma