Study of HPV Specific Immunotherapy in Participants With HPV Associated Head and Neck Squamous Cell Carcinoma

January 4, 2021 updated by: Inovio Pharmaceuticals

Prospective Study of HPV Specific Immunotherapy in Subjects With HPV Associated Head and Neck Squamous Cell Carcinoma (HNSCCa)

This is a Phase I/IIa, open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 DNA vaccine delivered by electroporation (EP) to participants with human papilloma virus (HPV) associated head and neck squamous cell cancer (HNSCC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase I/IIa, open-label, study to evaluate the safety, tolerability, and immunogenicity of INO-3112 [6 mg of VGX-3100 (2 separate DNA plasmids respectively encoding E6 and E7 proteins of HPV 16 and HPV 18) and 1 mg of INO-9012 (DNA plasmid encoding human interleukin 12)] delivered by electroporation (EP) in up to 25 (twenty-five) participants with HPV positive head and neck cancer. The immunotherapy was studied in the following two groups of participants:

  1. Participants who received immunotherapy before and after definitive surgery (Cohort I)
  2. Participants who received immunotherapy at least 2 months after chemoradiation therapy (Cohort II).

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Signed and dated written Ethics Committee approved informed consent.
  2. Age ≥18 years.

  3. Histologically confirmed HPV-positive (as assessed by p16 IHC or oncogenic HPV ISH or PCR) mucosal squamous cell head and neck cancer:

    • For pre-surgical participants, p16 positivity must be confirmed prior to the first dose.
    • For participants post-chemoradiation, HPV 16 and HPV 18 positivity must be confirmed prior to the first dose.
  4. 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), (Aspartate Aminotransferase) AST, (Alanine Aminotransferase) ALT within 2.5x institutional ULN, (Creatine Phosphokinase) CPK within 2.5 x ULN.
  5. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.

Exclusion Criteria:

  1. Anticipated concomitant immunosuppressive therapy (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids).
  2. Any concurrent condition requiring the continued use of systemic steroids (>10 mg prednisone or equivalent per day) or the use of immunosuppressive agents. All other corticosteroids must be discontinued at least 4 weeks prior to Day 0 of treatment.
  3. Administration of any vaccine within 6 weeks of enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Cohort 1: Surgery Cohort
Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device.
Biological: INO-3112
1.1 mL of INO-3112 (VGX-3100 + INO-9012) delivered intramuscularly (IM) followed immediately by electroporation (EP) with CELLECTRA™-5P device for a total of 4 doses of immunotherapy.
Other Names:
  • VGX-3100
  • INO-9012
Device: CELLECTRA™-5P
CELLECTRA™-5P device was used for EP following IM delivery of INO-3112 for a total of 4 doses of immunotherapy.
Other: Cohort 2: Chemoradiation
Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.
Biological: INO-3112
1.1 mL of INO-3112 (VGX-3100 + INO-9012) delivered intramuscularly (IM) followed immediately by electroporation (EP) with CELLECTRA™-5P device for a total of 4 doses of immunotherapy.
Other Names:
  • VGX-3100
  • INO-9012
Device: CELLECTRA™-5P
CELLECTRA™-5P device was used for EP following IM delivery of INO-3112 for a total of 4 doses of immunotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs)
Time Frame: Up to 6 months post last dose
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product. TEAE is defined as any AE with onset after the administration of study medication through the end-of-study follow-up, or any event that was present at baseline but worsened in intensity or was subsequently considered treatment-related by the Investigator through the end of the study. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life-threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful or requires inpatient hospitalization or prolongation of existing hospitalization.
Up to 6 months post last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Time Frame: Up to 6 months post last dose
Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.
Up to 6 months post last dose
E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA
Time Frame: Up to 6 months post last dose
Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.
Up to 6 months post last dose
Change From Baseline (CFB) in Combined HPV-16 and HPV-18 E6 and E7 Antigen-Specific Spot-Forming Units Per Million Peripheral Blood Mononuclear Cell (SFU/10^6 PBMC) as Assessed by Enzyme-Linked Immunosorbent Spot-Forming Assay (ELISpot)
Time Frame: Baseline up to 6 months post last dose
Baseline up to 6 months post last dose
Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry
Time Frame: At baseline and Week 2 post last dose
A flow cytometry assay called "lytic granule loading" was used to analyze CD8+ T cells specific for HPV-16 and CD8+ T cells specific for HPV-18 by evaluating the following markers: CD8, granzyme A (GrzA), granzyme B (GrzB), and perforin (Prf) co-expression with CD137, CD69, or CD38.
At baseline and Week 2 post last dose
Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry
Time Frame: At baseline and Week 2 post last dose
A flow cytometry assay called "lytic granule loading" was used to analyze CD8+ T cells specific for HPV-16 and CD8+ T cells specific for HPV-18 by evaluating the following markers: CD8, granzyme A (GrzA), granzyme B (GrzB), and perforin (Prf) co-expression with CD137, CD69, or CD38.
At baseline and Week 2 post last dose
Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
Time Frame: At screening and post-surgery
The difference in means (post-surgery minus screening) for tumor-infiltrating lymphocytes (TILs) such as CD8, FoxP3, and perforin was analyzed using immunohistochemistry staining techniques.
At screening and post-surgery
Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
Time Frame: At screening and post-surgery
The difference in means (post-surgery minus screening) for the CD8/FoxP3 ratio was analyzed using immunohistochemistry staining techniques.
At screening and post-surgery
Phenotype of Cultured TILs
Time Frame: Up to 6 months post last dose
Up to 6 months post last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inovio Pharmaceuticals

Collaborators

University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 13, 2014

Primary Completion (Actual)

January 23, 2017

Study Completion (Actual)

January 23, 2017

Study Registration Dates

First Submitted

June 10, 2014

First Submitted That Met QC Criteria

June 12, 2014

First Posted (Estimate)

June 13, 2014

Study Record Updates

Last Update Posted (Actual)

January 22, 2021

Last Update Submitted That Met QC Criteria

January 4, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HPV-005

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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