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

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

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.

Study Overview

• Status: Completed
• Conditions: Aerodigestive Precancerous Lesions and Malignancies
• Intervention / Treatment: Biological: INO-3106, INO-9012

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort I; 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
Experimental: Cohort II; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Time Frame
Time to new anti-cancer therapy	First dose to Week 26

Collaborators and Investigators

• Sponsor: Inovio Pharmaceuticals
• Collaborators: University of Pennsylvania

Publications and helpful links

Helpful Links

• Sponsor's Website

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: September 11, 2014
• First Submitted That Met QC Criteria: September 12, 2014
• First Posted (Estimate): September 16, 2014

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Squamous Cell Carcinoma; Human Papillomavirus; Aerodigestive Lesions and Malignancies
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: HPV-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO