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

Phase 1

Completed

• Conditions: Aerodigestive Precancerous Lesions and Malignancies
• Interventions: Biological: INO-3106, INO-9012

• Registration Number: NCT02241369
• Lead Sponsor: Inovio Pharmaceuticals

Brief Summary

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

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 Timeline

• Study Start: 2014-05
• Study First Submitted: 2014-09-11
• Study First Submitted QC: 2014-09-12
• Study First Posted: 2014-09-16
• Primary Completion: 2018-09
• Study Completion: 2018-09
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-15
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort II	INO-3106, INO-9012	6 mg of INO-3106 in combination with 1 mg of INO-9012, or at the MTD determined above at D0, Wk3, Wk6, Wk9
Cohort I	INO-3106, INO-9012	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);

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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
HPV6 specific Ig levels	Up to 6 months
Cytotoxic T cells in response to HPV6 specific immunotherapy by flow cytometry	Up to 6 months

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States