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

• Sponsor: Inovio Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02163057
• Collaborator: University of Pennsylvania (Other)
• Enrollment: 22
• Location: 1
• Arms: 2
• Actual Duration (Months): 29.4
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Squamous Cell Cancer	Biological: INO-3112; Device: CELLECTRA™-5P	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Study of HPV Specific Immunotherapy in Subjects With HPV Associated Head and Neck Squamous Cell Carcinoma (HNSCCa)
• Actual Study Start Date: Aug 13, 2014
• Actual Primary Completion Date: Jan 23, 2017
• Actual Study Completion Date: Jan 23, 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

1. E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) [Up to 6 months post last dose]

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

2. E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA [Up to 6 months post last dose]

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

3. 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]

4. 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]

   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.

5. 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]

   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.

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

7. Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC) [At screening and post-surgery]

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

8. Phenotype of Cultured TILs [Up to 6 months post last dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

2. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Inovio Pharmaceuticals
• University of Pennsylvania

Investigators

• Study Director: Jeffrey Skolnik, MD, Inovio Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 8, 2016

More Information

Additional Information:

• Sponsor's Website

Publications

• 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.
• Diehl MC, Lee JC, Daniels SE, Tebas P, Khan AS, Giffear M, Sardesai NY, Bagarazzi ML. Tolerability of intramuscular and intradermal delivery by CELLECTRA(®) 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.

• Responsible Party: Inovio Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02163057
• Other Study ID Numbers: HPV-005
• First Posted: Jun 13, 2014
• Last Update Posted: Jan 22, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Inovio Pharmaceuticals: Head and neck squamous cell cancer; Papillomavirus
• Additional relevant MeSH terms: Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Squamous Cell

Study Results

Participant Flow

Recruitment Details	Participants with a diagnosis of HPV associated head and neck squamous cell carcinoma were enrolled in the study between 13th August 2014 to 23rd January 2017.

Arm/Group Title	Cohort 1: Surgery Cohort	Cohort 2: Chemoradiation
Arm/Group Description	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.
Period Title: Overall Study
STARTED	6	16
COMPLETED	3	11
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Cohort 1: Surgery Cohort	Cohort 2: Chemoradiation	Total
Arm/Group Description	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.	Total of all reporting groups
Overall Participants	6	16	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.2 (4.26)	55.4 (10.26)	57.3 (9.43)
Sex: Female, Male (Count of Participants)
Female	0 0%	2 12.5%	2 9.1%
Male	6 100%	14 87.5%	20 90.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	16 100%	22 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 16.7%	2 12.5%	3 13.6%
White	5 83.3%	14 87.5%	19 86.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs)
Description	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.
Time Frame	Up to 6 months post last dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: Surgery Cohort	Cohort 2: Chemoradiation
Arm/Group Description	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.
Measure Participants	6	16
At least 1 TEAE	6 100%	15 93.8%
At least 1 Treatment-emergent SAE	2 33.3%	0 0%

2. Secondary Outcome

Title	E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Description	Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.
Time Frame	Up to 6 months post last dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1: Surgery Cohort	Cohort 2: Chemoradiation
Arm/Group Description	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.
Measure Participants	5	15
HPV-16 ELISA titer, 1st dose	3.6 (4.53)	0.4 (1.18)
HPV-16 ELISA titer, 2nd dose	2.2 (2.61)	0.0 (0.00)
HPV-16 ELISA titer, 3rd dose	2.6 (2.39)	1.2 (2.33)
HPV-16 ELISA titer, 4th dose	2.4 (3.44)	1.0 (2.42)
HPV-16 ELISA titer, Week 2 post last dose	2.8 (3.48)	2.3 (2.91)
HPV-16 ELISA titer, 1st long term follow-up	1.3 (2.51)	1.0 (2.42)
HPV-16 ELISA titer, 2nd long term follow-up	0.0 (0.00)	1.2 (2.63)
HPV-16 ELISA titer, 3rd long term follow-up	0.0 (0.00)	0.8 (2.40)
HPV-16 ELISA titer, 4th long term follow-up	0.0 (0.00)	1.4 (3.39)
HPV-16 ELISA titer, 5th long term follow-up	0.0 (0.00)	0.0 (0.00)
HPV-16 ELISA titer, 6th long term follow-up	3.1 (4.32)
HPV-16 ELISA titer, initial surgery	1.0 (2.24)
HPV-16 ELISA titer, surgery	0.0 (0.00)
HPV-16 ELISA titer, follow-up Week 2 post-surgery	4.6 (1.27)
HPV-16 ELISA titer, optional surgery	0.0 (NA)
HPV-16 ELISA titer, unscheduled visit	3.9 (NA)
HPV-16 ELISA titer, end of study follow-up	0.0 (0.00)	0.0 (0.00)
HPV-18 ELISA titer, 1st dose	0.0 (0.00)	0.4 (1.18)
HPV-18 ELISA titer, 2nd dose	0.0 (0.00)	0.7 (1.69)
HPV-18 ELISA titer, 3rd dose	0.0 (0.00)	0.8 (1.88)
HPV-18 ELISA titer, 4th dose	1.0 (2.24)	1.2 (2.12)
HPV-18 ELISA titer, Week 2 post last dose	0.0 (0.00)	3.0 (3.25)
HPV-18 ELISA titer, 1st long term follow-up	1.3 (2.51)	2.0 (3.04)
HPV-18 ELISA titer, 2nd long term follow-up	1.0 (2.24)	1.3 (2.09)
HPV-18 ELISA titer, 3rd long term follow-up	0.0 (0.00)	1.1 (2.28)
HPV-18 ELISA titer, 4th long term follow-up	0.0 (0.00)	1.7 (2.68)
HPV-18 ELISA titer, 5th long term follow-up	0.0 (0.00)	1.7 (2.89)
HPV-18 ELISA titer, 6th long term follow-up	6.1 (0.00)
HPV-18 ELISA titer, initial surgery	0.0 (0.00)
HPV-18 ELISA titer, surgery	0.0 (0.00)
HPV-18 ELISA titer, follow-up Week 2 post-surgery	0.0 (0.00)
HPV-18 ELISA titer, optional surgery	0.0 (NA)
HPV-18 ELISA titer, unscheduled visit	0.0 (NA)
HPV-18 ELISA titer, end of study follow-up	1.5 (3.05)	2.8 (3.01)

3. Secondary Outcome

Title	E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA
Description	Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.
Time Frame	Up to 6 months post last dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1: Surgery Cohort	Cohort 2: Chemoradiation
Arm/Group Description	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.
Measure Participants	5	15
HPV-16, 1st dose	0.0 (0.00)	0.4 (1.18)
HPV-16 ELISA titer, 2nd dose	0.0 (0.00)	0.5 (1.69)
HPV-16 ELISA titer, 3rd dose	1.2 (2.73)	2.1 (2.85)
HPV-16 ELISA titer, 4th dose	3.0 (3.06)	3.0 (3.41)
HPV-16 ELISA titer, Week 2 post last dose	2.8 (3.48)	3.3 (4.09)
HPV-16 ELISA titer, 1st long term follow-up	2.5 (3.03)	2.8 (3.63)
HPV-16 ELISA titer, 2nd long term follow-up	0.8 (1.75)	1.6 (3.28)
HPV-16 ELISA titer, 3rd long term follow-up	0.0 (0.00)	1.5 (3.24)
HPV-16 ELISA titer, 4th long term follow-up	0.0 (0.00)	0.8 (2.05)
HPV-16 ELISA titer, 5th long term follow-up	0.0 (0.00)	3.1 (5.43)
HPV-16 ELISA titer, 6th long term follow-up	4.2 (5.87)
HPV-16 ELISA titer, initial surgery	0.0 (0.00)
HPV-16 ELISA titer, surgery	0.0 (0.00)
HPV-16 ELISA titer, follow-up Week 2 post-surgery	0.0 (0.00)
HPV-16 ELISA titer, optional surgery	0.0 (NA)
HPV-16 ELISA titer, unscheduled visit	0.0 (NA)
HPV-16 ELISA titer, end of study follow-up	0.0 (0.00)	1.3 (2.45)
HPV-18 ELISA titer, 1st dose	0.0 (0.00)	0.5 (1.51)
HPV-18 ELISA titer, 2nd dose	2.5 (2.89)	0.3 (1.08)
HPV-18 ELISA titer, 3rd dose	2.7 (3.67)	1.3 (2.03)
HPV-18 ELISA titer, 4th dose	4.5 (4.17)	3.0 (3.21)
HPV-18 ELISA titer, Week 2 post last dose	8.0 (1.65)	4.2 (2.83)
HPV-18 ELISA titer, 1st long term follow-up	6.9 (2.44)	4.5 (3.41)
HPV-18 ELISA titer, 2nd long term follow-up	5.8 (3.98)	1.8 (3.13)
HPV-18 ELISA titer, 3rd long term follow-up	2.0 (2.77)	3.1 (3.79)
HPV-18 ELISA titer, 4th long term follow-up	0.0 (0.00)	2.5 (2.83)
HPV-18 ELISA titer, 5th long term follow-up	0.0 (0.00)	5.5 (4.80)
HPV-18 ELISA titer, 6th long term follow-up	8.3 (0.00)
HPV-18 ELISA titer, initial surgery	0.0 (0.00)
HPV-18 ELISA titer, surgery	2.4 (4.70)
HPV-18 ELISA titer, follow-up Week 2 post-surgery	1.3 (2.26)
HPV-18 ELISA titer, optional surgery	0.0 (NA)
HPV-18 ELISA titer, unscheduled visit	0.0 (NA)
HPV-18 ELISA titer, end of study follow-up	4.4 (5.29)	4.6 (3.03)

4. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1: Surgery Cohort	Cohort 2: Chemoradiation
Arm/Group Description	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.
Measure Participants	5	15
Baseline	20.3 (22.65)	11.7 (10.25)
CFB at 2nd dose	24.2 (34.56)	96.9 (118.41)
CFB at 3rd dose	15.0 (17.54)	158.9 (231.73)
CFB at 4th dose	50.3 (49.06)	263.6 (597.80)
CFB at Week 2 post last dose	68.3 (63.98)	354.7 (632.29)
CFB at 1st long term follow-up	182.2 (211.31)	128.8 (132.05)
CFB at 2nd long term follow-up	102.3 (140.03)	151.1 (94.32)
CFB at 3rd long term follow-up	127.6 (3.46)	113.2 (153.59)
CFB at 4th long term follow-up	41.4 (NA)	29.8 (28.11)
CFB at 5th long term follow-up	129.1 (19.87)	0.0 (NA)
CFB at 6th long term follow-up	141.7 (NA)	11.7 (NA)
CFB at follow-up Week 2 post-surgery	154.2 (168.50)
CFB at end of study follow-up	50.0 (42.75)	70.5 (87.09)

5. Secondary Outcome

Title	Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry
Description	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.
Time Frame	At baseline and Week 2 post last dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1: Surgery Cohort	Cohort 2: Chemoradiation
Arm/Group Description	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.
Measure Participants	5	15
CD8+CD137+GrzA+GrzB+Prf+, baseline	0.09 (0.124)	0.02 (0.039)
CD8+CD137+GrzA+GrzB+Prf+,CFB Week 2 post last dose	0.16 (0.230)	0.11 (0.188)
CD8+CD69+GrzA+GrzB+Prf+, baseline	0.00 (0.000)	0.17 (0.345)
CD8+CD69+GrzA+GrzB+Prf+, CFB Week 2 post last dose	0.48 (0.282)	0.20 (0.471)
CD8+CD38+GrzA+GrzB+Prf+, baseline	0.00 (0.000)	0.14 (0.163)
CD8+CD38+GrzA+GrzB+Prf+, CFB Week 2 post last dose	0.89 (0.457)	0.26 (0.555)

6. Secondary Outcome

Title	Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry
Description	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.
Time Frame	At baseline and Week 2 post last dose

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Cohort 1: Surgery Cohort	Cohort 2: Chemoradiation
Arm/Group Description	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.
Measure Participants	5	15
CD8+CD137+GrzA+GrzB+Prf+, baseline	0.00 (0.000)	0.05 (0.070)
CD8+CD137+GrzA+GrzB+Prf+,CFB Week 2 post last dose	0.09 (0.073)	0.07 (0.089)
CD8+CD69+GrzA+GrzB+Prf+, baseline	0.00 (0.000)	0.10 (0.158)
CD8+CD69+GrzA+GrzB+Prf+, CFB Week 2 post last dose	0.20 (0.283)	0.34 (0.540)
CD8+CD38+GrzA+GrzB+Prf+, baseline	0.00 (0.000)	0.06 (0.135)
CD8+CD38+GrzA+GrzB+Prf+, CFB Week 2 post last dose	0.73 (0.841)	0.36 (0.552)

7. Secondary Outcome

Title	Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
Description	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.
Time Frame	At screening and post-surgery

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: Surgery Cohort
Arm/Group Description	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.
Measure Participants	4
CD8	268.5
FoxP3	-79.8
Perforin	9.5

8. Secondary Outcome

Title	Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
Description	The difference in means (post-surgery minus screening) for the CD8/FoxP3 ratio was analyzed using immunohistochemistry staining techniques.
Time Frame	At screening and post-surgery

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: Surgery Cohort
Arm/Group Description	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.
Measure Participants	4
Mean (95% Confidence Interval) [ratio]	0.2

9. Secondary Outcome

Title	Phenotype of Cultured TILs
Time Frame	Up to 6 months post last dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort 1: Surgery Cohort	Cohort 2: Chemoradiation
Arm/Group Description	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.
Measure Participants	0	0

Adverse Events

Time Frame	Up to 6 months post last dose
Arm/Group Title	Cohort 1: Surgery Cohort		Cohort 2: Chemoradiation
Arm/Group Description	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.
All Cause Mortality
	Cohort 1: Surgery Cohort		Cohort 2: Chemoradiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/16 (0%)
Serious Adverse Events
	Cohort 1: Surgery Cohort		Cohort 2: Chemoradiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)		0/16 (0%)
Immune system disorders
Anaphylactic reaction	1/6 (16.7%)		0/16 (0%)
Injury, poisoning and procedural complications
Post procedural haemorrhage	1/6 (16.7%)		0/16 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/6 (16.7%)		0/16 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin neoplasm bleeding	1/6 (16.7%)		0/16 (0%)
Renal and urinary disorders
Acute kidney injury	1/6 (16.7%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: Surgery Cohort		Cohort 2: Chemoradiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		15/16 (93.8%)
Ear and labyrinth disorders
Tinnitus	1/6 (16.7%)		1/16 (6.3%)
Endocrine disorders
Hypothyroidism	1/6 (16.7%)		1/16 (6.3%)
Thyroiditis	1/6 (16.7%)		0/16 (0%)
Eye disorders
Diplopia	1/6 (16.7%)		0/16 (0%)
Retinal Detachment	1/6 (16.7%)		0/16 (0%)
Gastrointestinal disorders
Dry Mouth	2/6 (33.3%)		1/16 (6.3%)
Dysphagia	3/6 (50%)		1/16 (6.3%)
Eructation	0/6 (0%)		1/16 (6.3%)
Gastrooesophageal Reflux Disease	0/6 (0%)		3/16 (18.8%)
Glossodynia	1/6 (16.7%)		0/16 (0%)
Hypoaesthesia Oral	1/6 (16.7%)		0/16 (0%)
Nausea	1/6 (16.7%)		0/16 (0%)
Odynophagia	1/6 (16.7%)		0/16 (0%)
Oral Discomfort	0/6 (0%)		1/16 (6.3%)
Oral Pain	0/6 (0%)		1/16 (6.3%)
Salivary Duct Inflammation	1/6 (16.7%)		0/16 (0%)
Stomatitis	0/6 (0%)		1/16 (6.3%)
Tongue Discolouration	1/6 (16.7%)		0/16 (0%)
Tongue Oedema	1/6 (16.7%)		0/16 (0%)
Toothache	1/6 (16.7%)		0/16 (0%)
General disorders
Chest Pain	0/6 (0%)		1/16 (6.3%)
Fatigue	2/6 (33.3%)		1/16 (6.3%)
Injection Site Bruising	2/6 (33.3%)		3/16 (18.8%)
Injection Site Erythema	2/6 (33.3%)		5/16 (31.3%)
Injection Site Induration	0/6 (0%)		1/16 (6.3%)
Injection Site Pain	5/6 (83.3%)		10/16 (62.5%)
Injection Site Swelling	1/6 (16.7%)		4/16 (25%)
Localised Oedema	2/6 (33.3%)		0/16 (0%)
Mucosal Inflammation	1/6 (16.7%)		1/16 (6.3%)
Immune system disorders
Seasonal Allergy	0/6 (0%)		1/16 (6.3%)
Infections and infestations
Epididymitis	0/6 (0%)		1/16 (6.3%)
Folliculitis	1/6 (16.7%)		0/16 (0%)
Furuncle	2/6 (33.3%)		0/16 (0%)
Herpes Zoster	1/6 (16.7%)		0/16 (0%)
Oral Candidiasis	1/6 (16.7%)		2/16 (12.5%)
Oral Herpes	1/6 (16.7%)		0/16 (0%)
Staphylococcal Infection	1/6 (16.7%)		0/16 (0%)
Upper Respiratory Tract Infection	1/6 (16.7%)		0/16 (0%)
Urinary Tract Infection	0/6 (0%)		1/16 (6.3%)
Viral Upper Respiratory Tract Infection	1/6 (16.7%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Ankle Fracture	0/6 (0%)		1/16 (6.3%)
Procedural Pain	1/6 (16.7%)		0/16 (0%)
Investigations
Blood Creatinine Increased	1/6 (16.7%)		0/16 (0%)
Weight Decreased	2/6 (33.3%)		2/16 (12.5%)
Metabolism and nutrition disorders
Decreased Appetite	2/6 (33.3%)		1/16 (6.3%)
Dyslipidaemia	0/6 (0%)		1/16 (6.3%)
Hypomagnesaemia	1/6 (16.7%)		0/16 (0%)
Hyponatraemia	1/6 (16.7%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Joint Range Of Motion Decreased	0/6 (0%)		1/16 (6.3%)
Muscle Spasms	0/6 (0%)		1/16 (6.3%)
Muscle Twitching	1/6 (16.7%)		0/16 (0%)
Musculoskeletal Pain	1/6 (16.7%)		1/16 (6.3%)
Musculoskeletal Stiffness	1/6 (16.7%)		1/16 (6.3%)
Myalgia	0/6 (0%)		1/16 (6.3%)
Neck Pain	2/6 (33.3%)		0/16 (0%)
Pain In Extremity	0/6 (0%)		1/16 (6.3%)
Pain In Jaw	0/6 (0%)		1/16 (6.3%)
Trigger Finger	0/6 (0%)		1/16 (6.3%)
Trismus	1/6 (16.7%)		0/16 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic Naevus	0/6 (0%)		1/16 (6.3%)
Nervous system disorders
Dizziness	1/6 (16.7%)		1/16 (6.3%)
Dysgeusia	2/6 (33.3%)		1/16 (6.3%)
Hypoaesthesia	0/6 (0%)		2/16 (12.5%)
Neuropathy Peripheral	1/6 (16.7%)		1/16 (6.3%)
Paraesthesia	0/6 (0%)		2/16 (12.5%)
Peripheral Sensory Neuropathy	0/6 (0%)		1/16 (6.3%)
Restless Legs Syndrome	0/6 (0%)		1/16 (6.3%)
Psychiatric disorders
Depression	1/6 (16.7%)		0/16 (0%)
Renal and urinary disorders
Haematuria	0/6 (0%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/6 (16.7%)		0/16 (0%)
Dysphonia	3/6 (50%)		0/16 (0%)
Dyspnoea Exertional	1/6 (16.7%)		0/16 (0%)
Oropharyngeal Pain	1/6 (16.7%)		0/16 (0%)
Pharyngeal Oedema	1/6 (16.7%)		0/16 (0%)
Pleuritic Pain	0/6 (0%)		1/16 (6.3%)
Productive Cough	1/6 (16.7%)		0/16 (0%)
Skin and subcutaneous tissue disorders
Alopecia Areata	0/6 (0%)		1/16 (6.3%)
Dermatitis Contact	0/6 (0%)		1/16 (6.3%)
Dry Skin	0/6 (0%)		1/16 (6.3%)
Erythema	1/6 (16.7%)		0/16 (0%)
Night Sweats	0/6 (0%)		1/16 (6.3%)
Rash Maculo-Papular	1/6 (16.7%)		0/16 (0%)
Rash Papular	0/6 (0%)		1/16 (6.3%)
Skin Fibrosis	1/6 (16.7%)		0/16 (0%)
Skin Lesion	0/6 (0%)		1/16 (6.3%)
Surgical and medical procedures
Skin Neoplasm Excision	0/6 (0%)		1/16 (6.3%)
Vascular disorders
Arteriosclerosis	0/6 (0%)		1/16 (6.3%)
Hypertension	1/6 (16.7%)		0/16 (0%)
Hypotension	1/6 (16.7%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.