Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

All Drugs and Chemicals

Immunomodulating Agents

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.

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.

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.

INO-3112

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

CELLECTRA™-5P

Jeffrey Skolnik, MD

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).

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

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

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.

Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.

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.

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.

The difference in means (post-surgery minus screening) for the CD8/FoxP3 ratio was analyzed using immunohistochemistry staining techniques.

University of Pennsylvania

Inovio Pharmaceuticals

Cohort 1: Surgery Cohort

Cohort 2: Chemoradiation

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Safety population included all participants who received at least one dose of study treatment plus EP.

Study Director

At least 1 TEAE

At least 1 Treatment-emergent SAE

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

HPV-16 ELISA titer, 1st dose

HPV-16 ELISA titer, 2nd dose

HPV-16 ELISA titer, 3rd dose

HPV-16 ELISA titer, 4th dose

HPV-16 ELISA titer, Week 2 post last dose

HPV-16 ELISA titer, 1st long term follow-up

HPV-16 ELISA titer, 2nd long term follow-up

HPV-16 ELISA titer, 3rd long term follow-up

HPV-16 ELISA titer, 4th long term follow-up

HPV-16 ELISA titer, 5th long term follow-up

HPV-16 ELISA titer, 6th long term follow-up

HPV-16 ELISA titer, initial surgery

HPV-16 ELISA titer, surgery

HPV-16 ELISA titer, follow-up Week 2 post-surgery

HPV-16 ELISA titer, optional surgery

HPV-16 ELISA titer, unscheduled visit

HPV-16 ELISA titer, end of study follow-up

HPV-18 ELISA titer, 1st dose

HPV-18 ELISA titer, 2nd dose

HPV-18 ELISA titer, 3rd dose

HPV-18 ELISA titer, 4th dose

HPV-18 ELISA titer, Week 2 post last dose

HPV-18 ELISA titer, 1st long term follow-up

HPV-18 ELISA titer, 2nd long term follow-up

HPV-18 ELISA titer, 3rd long term follow-up

HPV-18 ELISA titer, 4th long term follow-up

HPV-18 ELISA titer, 5th long term follow-up

HPV-18 ELISA titer, 6th long term follow-up

HPV-18 ELISA titer, initial surgery

HPV-18 ELISA titer, surgery

HPV-18 ELISA titer, follow-up Week 2 post-surgery

HPV-18 ELISA titer, optional surgery

HPV-18 ELISA titer, unscheduled visit

HPV-18 ELISA titer, end of study follow-up

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™ device.

Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™ device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy.

Assigned Number of Doses (ANoD) population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.

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

HPV-16, 1st dose

ANoD population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.

E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA

Baseline

CFB at 2nd dose

CFB at 3rd dose

CFB at 4th dose

CFB at Week 2 post last dose

CFB at 1st long term follow-up

CFB at 2nd long term follow-up

CFB at 3rd long term follow-up

CFB at 4th long term follow-up

CFB at 5th long term follow-up

CFB at 6th long term follow-up

CFB at follow-up Week 2 post-surgery

CFB at end of study follow-up

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)

CD8+CD137+GrzA+GrzB+Prf+, baseline

CD8+CD137+GrzA+GrzB+Prf+,CFB Week 2 post last dose

CD8+CD69+GrzA+GrzB+Prf+, baseline

CD8+CD69+GrzA+GrzB+Prf+, CFB Week 2 post last dose

CD8+CD38+GrzA+GrzB+Prf+, baseline

CD8+CD38+GrzA+GrzB+Prf+, CFB Week 2 post last dose

Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry

Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry

FoxP3

Perforin

ANoD population included all participants who received their assigned number of doses of study treatment plus EP.

Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)

Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)

Data was not collected due to lack of recoverable samples sufficient for analysis

Phenotype of Cultured TILs

Overall Study

Spots Global Cancer Trial Database for Study of HPV Specific Immunotherapy in Participants With HPV Associated Head and Neck Squamous Cell Carcinoma

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