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

NCT02163057 | Completed Phase 1 Results FDA Drug FDA Device

• 1 other identifier: HPV-005
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Head and Neck Squamous Cell Cancer

Keywords

Head and neck squamous cell cancer; Papillomavirus

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs)

  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 Outcomes (8)

• E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

  Up to 6 months post last dose

• E7 Antigen Specific Anti-HPV-16/18 Antibody Titers 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)

  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

  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

  At baseline and Week 2 post last dose

Study Arms (2)

Cohort 1: Surgery Cohort

OTHER

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; Device: CELLECTRA™-5P

Cohort 2: Chemoradiation

OTHER

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; Device: CELLECTRA™-5P

Interventions

INO-3112 BIOLOGICAL

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.

Also known as: VGX-3100, INO-9012

Cohort 1: Surgery Cohort; Cohort 2: Chemoradiation

CELLECTRA™-5P DEVICE

CELLECTRA™-5P device was used for EP following IM delivery of INO-3112 for a total of 4 doses of immunotherapy.

Cohort 1: Surgery Cohort; Cohort 2: Chemoradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated written Ethics Committee approved informed consent.
• Age ≥18 years.
• 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.
• 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.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.

You may not qualify if:

• Anticipated concomitant immunosuppressive therapy (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids).
• 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.
• Administration of any vaccine within 6 weeks of enrollment.

Sponsors & Collaborators

• Inovio Pharmaceuticals: lead
• University of Pennsylvania: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Bagarazzi ML, Yan J, Morrow MP, Shen X, Parker RL, Lee JC, Giffear M, Pankhong P, Khan AS, Broderick KE, Knott C, Lin F, Boyer JD, Draghia-Akli R, White CJ, Kim JJ, Weiner DB, Sardesai NY. Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med. 2012 Oct 10;4(155):155ra138. doi: 10.1126/scitranslmed.3004414.

  PMID: 23052295 BACKGROUND

• Diehl MC, Lee JC, Daniels SE, Tebas P, Khan AS, Giffear M, Sardesai NY, Bagarazzi ML. Tolerability of intramuscular and intradermal delivery by CELLECTRA((R)) adaptive constant current electroporation device in healthy volunteers. Hum Vaccin Immunother. 2013 Oct;9(10):2246-52. doi: 10.4161/hv.24702. Epub 2013 Jun 4.

  PMID: 24051434 BACKGROUND

Related Links

• Sponsor's Website

MeSH Terms

Interventions

MEDI0457; VGX-3100; rocakinogene sifuplasmid

Results Point of Contact

• Title: Study Director
• Organization: Inovio Pharmaceuticals

clinical.trials@inovio.com

267-440-4237

Study Officials

• Jeffrey Skolnik, MD

  Inovio Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: June 13, 2014
• Study Start: August 13, 2014
• Primary Completion: January 23, 2017
• Study Completion: January 23, 2017
• Last Updated: January 22, 2021
• Results First Posted: December 23, 2020

Record last verified: 2021-01

Locations

US (1)