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

Inovio Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Aerodigestive Precancerous Lesions and Malignancies

Treatments: Biological: INO-3106, INO-9012

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02241369

HPV-006

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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3 participants in 2 patient groups

Cohort I

Experimental group

Description:

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);

Treatment:

Biological: INO-3106, INO-9012

Cohort II

Experimental group

Description:

6 mg of INO-3106 in combination with 1 mg of INO-9012, or at the MTD determined above at D0, Wk3, Wk6, Wk9

Treatment:

Biological: INO-3106, INO-9012