A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer

• Sponsor: Inovio Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02172911
• Collaborator: (none)
• Enrollment: 10
• Locations: 3
• Arms: 2
• Actual Duration (Months): 39.1
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 DNA vaccines delivered by electroporation (EP) to female participants with HPV-16 and/or 18-positive cervical carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Cervical 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 [VGX-3100 and INO-9012] delivered intramuscularly by electroporation in approximately 30 female participants with biopsy-proven, Stage IB-IVB inoperable invasive cervical carcinoma associated with HPV 16 and/or 18 who have completed treatment with standard chemoradiation therapy with curative intent (Cohort I) or in participants with persistent and/or recurrent cervical cancer associated with HPV 16 and/or 18 following salvage therapy (Cohort II).

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/IIA, Open-Label, Safety, Tolerability, and Immunogenicity Study of INO-3112 Delivered by Electroporation (EP) in Women With Cervical Cancer After Chemoradiation for Newly Diagnosed Disease or Therapy for Recurrent and/or Persistent Disease
• Actual Study Start Date: Jun 6, 2014
• Actual Primary Completion Date: Sep 7, 2017
• Actual Study Completion Date: Sep 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort I: INO-3112: Curative Intent Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Biological: INO-3112; 1.1 mL intramuscular (IM) injection of INO-3112 (VGX-3100 + INO-9012) was administered followed immediately by electroporation (EP) with CELLECTRA™-5P on Day 0, Week 4, Week 8, and Week 12.; Other Names: VGX-3100 INO-9012 ; Device: CELLECTRA™-5P; CELLECTRA™-5P was used for EP following IM delivery of INO-3112 on Day 0, Week 4, Week 8, and Week 12.
Experimental: Cohort II: INO-3112: Salvage Therapy Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Biological: INO-3112; 1.1 mL intramuscular (IM) injection of INO-3112 (VGX-3100 + INO-9012) was administered followed immediately by electroporation (EP) with CELLECTRA™-5P on Day 0, Week 4, Week 8, and Week 12.; Other Names: VGX-3100 INO-9012 ; Device: CELLECTRA™-5P; CELLECTRA™-5P was used for EP following IM delivery of INO-3112 on Day 0, Week 4, Week 8, and Week 12.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE) [Up to 36 weeks]

   An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug.

2. Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) [Up to 36 weeks]

   An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug. The severity of TEAEs was assessed by the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE,v 4.03). TEAEs were graded on a 5-point scale where 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Potentially life-threatening and 5 = Death.

3. Percentage of Participants With Injection Site Reactions [Up to 36 weeks]

   Injection site reactions and administration site pain were evaluated starting 30 minutes following injection/EP. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' (Food and Drug Administration [FDA] Guidance for Industry, September 2007). Local reaction to the injectable product such as pain, tenderness, erythema/redness and induration/swelling were graded on a 4-point scale where: 1 = Mild, 2 = Moderate, 3 = Severe and 4 = Potentially life-threatening.

4. Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria [Up to 36 weeks]

5. Change From Baseline in Hematocrit at the Indicated Time Points [Baseline and Week 4, 8,12,16,24, 32 and 48]

   Clinical laboratory parameters (hematology, serum chemistry, and creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

6. Change From Baseline in Hemoglobin at the Indicated Time Points [Baseline and Weeks 4, 8,12,16,24, 32 and 48]

   Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

7. Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points [Baseline and Weeks 4, 8,12,16,24, 32 and 48]

   Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Hematology parameters analyzed for this outcome measure included: white blood cell (WBC) count, count of lymphocytes (L), monocytes (M) and neutrophils (N).

8. Change From Baseline in Platelet Count at the Indicated Time Points [Baseline and Weeks 4,8,12,16,24,32 and 48]

   Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

9. Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points [Baseline and Weeks 4 and 8]

   Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

10. Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points [Baseline and Weeks 4,8,12 and 16]

    Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Clinical chemistry parameter assessed in this outcome measure included alkaline phosphatase (ALP), alanine amino transferase (ALT) and aspartate amino transferase (AST).

11. Change From Baseline in Bicarbonate, Glucose, Blood Urea Nitrogen (BUN), Calcium (Ca), Chloride (Cl), Potassium (K), Magnesium (Mg) and Sodium (Na) at the Indicated Time Points [Baseline and Weeks 4,8,12 and 16]

    Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

12. Change From Baseline in Albumin and Total Protein at the Indicated Time Points [Baseline and Weeks 4,8,12 and 16]

    Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

13. Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points [Baseline and Week 16]

    Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

14. Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points [Baseline and Weeks 4, 8,12 and 16]

    Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

Secondary Outcome Measures

1. Change From Baseline in the Combined HPV-16 and HPV-18 E6 and E7 Antigen Specific Spot-Forming Units Per Million Peripheral Blood Mononuclear Cell (SFU/10^6 PBMC) [Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48]

   Whole blood and serum samples to be tested for antibodies to the human papillomavirus (HPV) E6 and E7 proteins and/or T-lymphocytes producing interferon-gamma (IFN-γ) elicited by INO-3112 were assessed by enzyme-linked immunosorbent spot-forming assay (ELISpot).

2. E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) [Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48]

   Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components.

3. E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA [Baseline and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 36, 40 and 48]

   Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Written informed consent.

2. Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix. Not accepted are small cell, clear cell and other rare variants of the classical adenocarcinoma.

3. Histologically confirmed, Stage IB-IVB, invasive cervical carcinoma associated with HPV 16 and/or 18 and meet the following eligibility criteria for either Cohort 1 or Cohort 2.

4. Cohort 1

• Newly diagnosed inoperable cervical cancer treated with chemoradiation therapy with curative intent and life expectancy of at least 12 months as assessed by the investigator

• No CNS/spinal metastases

• Able to initiate study treatment within 2 weeks of completion of last chemoradiation treatment

1. Cohort 2

• Persistent and/or recurrent cervical cancer

• No CNS/spinal metastases

• Able to initiate study treatment at least 2 weeks but no more than 4 weeks after completion of salvage therapy

• Life expectancy of at least 12 months as assessed by the investigator

1. Electrocardiogram (ECG) with no clinically significant findings.

2. Chemistry, liver function tests, renal function, total CPK and hematology lab results must be ≤ Grade 1 at the time of screening.

3. Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 1.

4. Adequate venous access for repeated blood sampling according to the study schedule.

5. Women of child-bearing potential must have a negative serum pregnancy test and agree to remain sexually abstinent, have a partner who is sterile (i.e., vasectomy), or use two medically effective methods of contraception (e.g., oral contraception, barrier methods, spermicide, intrauterine device [IUD]).

6. Able and willing to comply with all study procedures.

Exclusion Criteria:

1. Pregnancy or breastfeeding.

2. History of previous therapeutic HPV vaccination.

3. Prior exposure to an investigational agent or device within 30 days of signing the ICF. Of note, the participant may participate in observational studies.

4. Positive serological test for HIV, Hep B or Hep C or history of HIV infection, Hepatitis B or Hepatitis C (women with cured HCV will be allowed; participant must have had a serologic test performed within 12 months of informed consent).

5. Prior major surgery from which the participant has not yet recovered to baseline.

6. High medical risks because of non-malignant systemic disease or with active uncontrolled infection.

7. Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin.

8. Congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease.

9. Use of topical corticosteroids at or near the intended administration site.

10. Any cardiac pre-excitation syndromes (such as Wolff-Parkinson-White).

11. History of seizures (unless seizure free for 5 years).

12. Tattoos or scars within 2 cm of the intended site of injection or if there is implanted metal within the same limb. Any device implanted in the chest (e.g., cardiac pacemaker or defibrillator) excludes the use of the deltoid muscle on the same side of the body.

13. Active drug or alcohol use or dependence.

14. Imprisonment or compulsory detainment for treatment of either a psychiatric or physical (i.e. infectious disease) illness.

15. History of immunosuppressive or autoimmune disease.

16. Any other illnesses or conditions that in the opinion of the investigator may affect the safety of the participant or limit the evaluation of a participant or any study endpoint.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Medical Center	Chicago	Illinois	United States	60637
2	University of Michigan	Ann Arbor	Michigan	United States	48109
3	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Inovio Pharmaceuticals

Investigators

• Study Director: Jeffrey Skolnik, MD, Inovio Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 27, 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: NCT02172911
• Other Study ID Numbers: HPV-004
• First Posted: Jun 24, 2014
• Last Update Posted: Feb 21, 2021
• Last Verified: Feb 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: Cervical cancer; Papillomavirus; Chemoradiation; Recurrent cervical cancer; Persistent cervical cancer
• Additional relevant MeSH terms: Uterine Cervical Neoplasms

Study Results

Participant Flow

Recruitment Details	Female participants with cervical cancer after chemoradiation for newly diagnosed disease or therapy for recurrent and/or persistent disease were enrolled in 2 study sites between 6th June 2014 to 7th September 2017.

Arm/Group Title	Cohort I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Period Title: Overall Study
STARTED	7	3
COMPLETED	6	1
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Cohort I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy	Total
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Total of all reporting groups
Overall Participants	7	3	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.9 (11.63)	41.7 (14.64)	46.0 (12.11)
Sex/Gender, Customized (Count of Participants)
Female	7 100%	3 100%	10 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 28.6%	1 33.3%	3 30%
Not Hispanic or Latino	5 71.4%	2 66.7%	7 70%
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 14.3%	1 33.3%	2 20%
White	5 71.4%	1 33.3%	6 60%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 14.3%	1 33.3%	2 20%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)
Description	An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug.
Time Frame	Up to 36 weeks

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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Number (95% Confidence Interval) [percentage of participants]	100 1428.6%	100 3333.3%

2. Primary Outcome

Title	Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03)
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug. The severity of TEAEs was assessed by the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE,v 4.03). TEAEs were graded on a 5-point scale where 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Potentially life-threatening and 5 = Death.
Time Frame	Up to 36 weeks

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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Anaemia	0 0%	33.3 1110%
Disseminated Intravascular Coagulation	0 0%	33.3 1110%
Abdominal Pain	14.3 204.3%	0 0%
Intestinal Perforation	0 0%	33.3 1110%
Pneumonia	14.3 204.3%	0 0%
Pathological Fracture	0 0%	33.3 1110%

3. Primary Outcome

Title	Percentage of Participants With Injection Site Reactions
Description	Injection site reactions and administration site pain were evaluated starting 30 minutes following injection/EP. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' (Food and Drug Administration [FDA] Guidance for Industry, September 2007). Local reaction to the injectable product such as pain, tenderness, erythema/redness and induration/swelling were graded on a 4-point scale where: 1 = Mild, 2 = Moderate, 3 = Severe and 4 = Potentially life-threatening.
Time Frame	Up to 36 weeks

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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Injection Site Bruising	28.6 408.6%	33.3 1110%
Injection Site Discolouration	0 0%	33.3 1110%
Injection Site Erythema	14.3 204.3%	0 0%
Injection Site Haemorrhage	14.3 204.3%	0 0%
Injection Site Pain	14.3 204.3%	66.7 2223.3%
Injection Site Swelling	14.3 204.3%	33.3 1110%

4. Primary Outcome

Title	Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria
Time Frame	Up to 36 weeks

Outcome Measure Data

Analysis Population Description

The above-mentioned outcome could not be assessed as no data were captured that reflect the expected rates of acute gastrointestinal, genitourinary or other chemoradiation side effects, in order to compare those collected on this study with those from prior studies. While adverse event data related to study therapy were captured, these were not graded per acute radiation morbidity score because of the above-noted limitation. No comparison was thus possible that would reflect rates expected.

Arm/Group Title	Cohort I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	0	0

5. Primary Outcome

Title	Change From Baseline in Hematocrit at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, and creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.
Time Frame	Baseline and Week 4, 8,12,16,24, 32 and 48

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Baseline	30.87 (3.118)	35.03 (5.016)
Change from Baseline at Week 4	1.63 (2.553)	-2.10 (2.800)
Change from Baseline at Week 8	3.49 (2.805)	-5.90 (6.505)
Change from Baseline at Week 12	5.73 (3.722)	1.60 (NA)
Change from Baseline at Week 16	5.97 (3.288)	2.10 (NA)
Change from Baseline at Week 24	5.10 (NA)
Change from Baseline at Week 32	4.80 (NA)
Change from Baseline at Week 48	4.70 (NA)

6. Primary Outcome

Title	Change From Baseline in Hemoglobin at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.
Time Frame	Baseline and Weeks 4, 8,12,16,24, 32 and 48

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Baseline	103.29 (10.339)	112.00 (22.517)
Change from Baseline at Week 4	5.57 (10.048)	-7.00 (9.165)
Change from Baseline at Week 8	11.14 (12.402)	-19.00 (24.042)
Change from Baseline at Week 12	18.29 (13.889)	4.00 (NA)
Change from Baseline at Week 16	20.29 (11.086)	8.00 (NA)
Change from Baseline at Week 24	17.00 (NA)
Change from Baseline at Week 32	8.00 (NA)
Change from Baseline at Week 48	7.00 (NA)

7. Primary Outcome

Title	Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Hematology parameters analyzed for this outcome measure included: white blood cell (WBC) count, count of lymphocytes (L), monocytes (M) and neutrophils (N).
Time Frame	Baseline and Weeks 4, 8,12,16,24, 32 and 48

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
L, Baseline	0.93 (0.522)	0.70 (0.400)
L,Change from Baseline at Week 4	-0.11 (0.261)	0.00 (0.200)
L,Change from Baseline at Week 8	-0.04 (0.251)	-0.10 (0.141)
L, Change from Baseline at Week 12	-0.10 (0.283)	-0.20 (NA)
L, Change from Baseline at Week 16	0.01 (0.254)	-0.20 (NA)
L, Change From Baseline at Week 24	0.20 (NA)
L, Change from Baseline at Week 32	-0.50 (NA)
L, Change from Baseline at Week 48	-0.40 (NA)
M, Baseline	0.39 (0.121)	0.30 (0.100)
M,Change from Baseline at Week 4	-0.06 (0.172)	0.07 (0.153)
M,Change from Baseline at Week 8	-0.03 (0.138)	0.05 (0.212)
M,Change from Baseline at Week 12	-0.03 (0.138)	0.10 (NA)
M,Change from Baseline at Week 16	-0.07 (0.160)	0.10 (NA)
M,Change from Baseline at Week 24	0.00 (NA)
M,Change from Baseline at Week 32	-0.40 (NA)
M,Change from Baseline at Week 48	-0.20 (NA)
N, Baseline	2.60 (2.129)	4.03 (0.551)
N,Change from Baseline at Week 4	0.43 (0.964)	0.37 (1.266)
N,Change from Baseline at Week 8	0.09 (1.188)	0.85 (0.212)
N,Change from Baseline at Week 12	-0.03 (0.138)	0.10 (NA)
N,Change from Baseline at Week 16	-0.07 (0.160)	0.10 (NA)
N,Change from Baseline at Week 24	0.00 (NA)
N,Change from Baseline at Week 32	-0.40 (NA)
N,Change from Baseline at Week 48	-0.20 (NA)
WBC, Baseline	4.20 (2.239)	5.30 (0.721)
WBC, Change from Baseline at Week 4	0.33 (0.966)	0.40 (1.114)
WBC, Change from Baseline at Week 8	0.27 (1.237)	0.85 (0.212)
WBC, Change from Baseline at Week 12	0.01 (1.771)	0.40 (NA)
WBC, Change from Baseline at Week 16	0.66 (1.279)	1.40 (NA)
WBC, Change from Baseline at Week 24	0.90 (NA)
WBC, Change from Baseline at Week 32	-0.40 (NA)
WBC, Change from Baseline at Week 48	-0.30 (NA)

8. Primary Outcome

Title	Change From Baseline in Platelet Count at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.
Time Frame	Baseline and Weeks 4,8,12,16,24,32 and 48

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Platelet Count, Baseline	259.86 (46.674)	271.33 (73.704)
Platelet Count, Change from Baseline at Week 4	-45.29 (55.479)	26.00 (48.754)
Platelet Count, Change from Baseline at Week 8	-40.57 (39.327)	93.00 (84.853)
Platelet Count, Change from Baseline at Week 12	-41.00 (61.563)	37.00 (NA)
Platelet Count, Change from Baseline at Week 16	-32.86 (49.911)	2.00 (NA)
Platelet Count, Change From Baseline at Week 24	-17.00 (NA)
Platelet Count, Change from Baseline at Week 32	-68.00 (NA)
Platelet Count, Change from Baseline at Week 48	-73.00 (NA)

9. Primary Outcome

Title	Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.
Time Frame	Baseline and Weeks 4 and 8

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
RBC Count, Baseline	3.34 (0.382)	3.97 (0.586)
RBC Count, Change from Baseline at Week 4	0.07 (0.355)	-0.23 (0.351)
RBC Count, Change from Baseline at Week 8	0.23 (0.386)	-0.55 (0.778)

10. Primary Outcome

Title	Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Clinical chemistry parameter assessed in this outcome measure included alkaline phosphatase (ALP), alanine amino transferase (ALT) and aspartate amino transferase (AST).
Time Frame	Baseline and Weeks 4,8,12 and 16

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
ALP, Baseline	73.29 (26.606)	81.33 (10.017)
ALP, Change from Baseline at Week 4	0.20 (13.989)	14.67 (21.779)
ALP, Change from Baseline at Week 8	3.00 (20.273)	54.00 (65.054)
ALP, Change from Baseline at Week 12	4.00 (26.448)	0.00 (NA)
ALP, Change from Baseline at Week 16	8.60 (22.233)	1.00 (NA)
ALT, Baseline	20.14 (6.793)	13.00 (9.849)
ALT, Change from Baseline at Week 4	4.60 (13.353)	-3.67 (11.590)
ALT, Change from Baseline at Week 8	-5.00 (4.950)	-4.50 (14.849)
ALT, Change from Baseline at Week 12	-1.60 (6.229)	-14.00 (NA)
ALT, Change from Baseline at Week 16	-2.20 (3.768)	-15.00 (NA)
AST, Baseline	22.71 (6.945)	17.00 (7.937)
AST, Change from Baseline at Week 4	3.20 (8.526)	-5.67 (11.547)
AST, Change from Baseline at Week 8	-3.80 (6.340)	-5.00 (14.142)
AST, Change from Baseline at Week 12	1.20 (13.461)	-15.00 (NA)
AST, Change from Baseline at Week 16	-2.80 (4.658)	-16.00 (NA)

11. Primary Outcome

Title	Change From Baseline in Bicarbonate, Glucose, Blood Urea Nitrogen (BUN), Calcium (Ca), Chloride (Cl), Potassium (K), Magnesium (Mg) and Sodium (Na) at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.
Time Frame	Baseline and Weeks 4,8,12 and 16

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Bicarbonate, Baseline	25.00 (1.633)	24.33 (2.082)
Bicarbonate, Change from Baseline at Week 4	0.00 (1.000)	3.33 (0.577)
Bicarbonate, Change from Baseline at Week 8	-0.60 (2.074)	0.00 (2.828)
Bicarbonate, Change from Baseline at Week 12	-1.40 (0.548)	2.00 (NA)
Bicarbonate, Change from Baseline at Week 16	-0.40 (1.140)	4.00 (NA)
Glucose, Baseline	6.90 (2.994)	5.25 (1.042)
Glucose, Change from Baseline at Week 4	-0.60 (0.736)	1.18 (0.946)
Glucose, Change from Baseline at Week 8	-0.57 (0.839)	2.69 (2.237)
Glucose, Change from Baseline at Week 12	-0.78 (0.755)	0.39 (NA)
Glucose, Change from Baseline at Week 16	-0.46 (0.308)	-1.44 (NA)
BUN, Baseline	4.18 (1.897)	4.17 (1.687)
BUN, Change from Baseline at Week 4	0.86 (1.485)	-1.07 (1.071)
BUN, Change from Baseline at Week 8	0.50 (1.568)	0.18 (0.757)
BUN, Change from Baseline at Week 12	1.87 (3.085)	-1.79 (NA)
BUN, Change from Baseline at Week 16	1.29 (1.686)	-0.71 (NA)
Ca, Baseline	2.33 (0.089)	2.37 (0.014)
Ca, Change from Baseline at Week 4	0.05 (0.077)	-0.06 (0.104)
Ca, Change from Baseline at Week 8	0.02 (0.045)	-0.16 (0.088)
Ca, Change from Baseline at Week 12	0.01 (0.086)	-0.08 (NA)
Ca, Change from Baseline at Week 16	0.04 (0.121)	-0.15 (NA)
Cl, Baseline	91.57 (28.757)	100.00 (3.464)
Cl, Change from Baseline at Week 4	15.40 (34.530)	-1.00 (2.646)
Cl, Change from Baseline at Week 8	14.60 (35.494)	-1.00 (1.414)
Cl, Change from Baseline at Week 12	14.00 (34.785)	1.00 (NA)
Cl, Change from Baseline at Week 16	14.40 (33.923)	0.00 (NA)
K, Baseline	4.20 (0.383)	4.37 (0.252)
K, Change from Baseline at Week 4	-0.16 (0.503)	-0.43 (1.305)
K, Change from Baseline at Week 8	-0.06 (0.391)	-0.65 (1.061)
K, Change from Baseline at Week 12	-0.02 (0.466)	-0.70 (NA)
K, Change from Baseline at Week 16	-0.14 (0.365)	-1.00 (NA)
Mg, Baseline	0.41 (NA)
Na, Baseline	141.29 (3.147)	138.67 (1.528)
Na, Change from Baseline at Week 4	0.00 (2.915)	1.67 (4.726)
Na, Change from Baseline at Week 8	-0.20 (1.924)	-0.50 (3.536)
Na, Change from Baseline at Week 12	-1.20 (2.280)	4.00 (NA)
Na, Change from Baseline at Week 16	-0.60 (1.517)	3.00 (NA)

12. Primary Outcome

Title	Change From Baseline in Albumin and Total Protein at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.
Time Frame	Baseline and Weeks 4,8,12 and 16

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Albumin, Baseline	42.00 (2.000)	40.33 (3.215)
Albumin, Change from Baseline at Week 4	-1.00 (1.000)	-1.00 (1.000)
Albumin, Change from Baseline at Week 8	0.80 (1.304)	-2.50 (3.536)
Albumin, Change from Baseline at Week 12	0.60 (2.191)	-2.00 (NA)
Albumin, Change from Baseline at Week 16	1.00 (1.871)	-1.00 (NA)
Total protein, Baseline	68.86 (4.488)	73.67 (3.215)
Total protein, Change from Baseline at Week 4	1.20 (2.168)	-2.67 (3.215)
Total protein, Change from Baseline at Week 8	2.80 (4.087)	-5.50 (3.536)
Total protein, Change from Baseline at Week 12	2.20 (5.805)	-2.00 (NA)
Total protein, Change from Baseline at Week 16	3.20 (5.357)	-2.00 (NA)

13. Primary Outcome

Title	Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
CPK, Baseline	46.9 (9.30)	42.7 (15.50)
CPK, Change from Baseline at Week 16	18.8 (15.80)	30.0 (NA)

14. Primary Outcome

Title	Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points
Description	Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase [CPK]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.
Time Frame	Baseline and Weeks 4, 8,12 and 16

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose 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 I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Creatinine, Baseline	66.93 (16.817)	70.72 (8.840)
Creatinine, Change from Baseline at Week 4	5.83 (7.543)	2.95 (5.104)
Creatinine, Change from Baseline at Week 8	-1.59 (7.193)	8.84 (12.502)
Creatinine, Change from Baseline at Week 12	6.01 (8.442)	-17.68 (NA)
Creatinine, Change from Baseline at Week 16	3.36 (8.015)	-8.84 (NA)
Total Bilirubin, Baseline	7.82 (4.922)	6.84 (4.524)
Total Bilirubin, Change from Baseline at Week 4	-1.71 (4.837)	-1.71 (2.962)
Total Bilirubin, Change from Baseline at Week 8	-1.37 (4.083)	-1.71 (4.837)
Total Bilirubin, Change from Baseline at Week 12	-1.03 (5.353)	0.00 (NA)
Total Bilirubin, Change from Baseline at Week 16	-0.00 (6.283)	0.00 (NA)

15. Secondary Outcome

Title	Change From Baseline in the Combined HPV-16 and HPV-18 E6 and E7 Antigen Specific Spot-Forming Units Per Million Peripheral Blood Mononuclear Cell (SFU/10^6 PBMC)
Description	Whole blood and serum samples to be tested for antibodies to the human papillomavirus (HPV) E6 and E7 proteins and/or T-lymphocytes producing interferon-gamma (IFN-γ) elicited by INO-3112 were assessed by enzyme-linked immunosorbent spot-forming assay (ELISpot).
Time Frame	Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat (mITT) population included all participants receiving at least one study treatment plus EP as assigned. Number analyzed is the number of participants with data available for analysis at a specified time-point.

Arm/Group Title	Cohort I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
Baseline	8.6 (6.03)	6.7 (2.89)
Increase from Baseline at Week 2	1.7 (2.35)
Increase from Baseline at Week 4	26.4 (29.84)	2.5 (3.54)
Increase from Baseline at Week 6	20.0 (NA)	24.2 (12.96)
Increase from Baseline at Week 8	68.3 (49.50)	0.0 (0.0)
Increase from Baseline at Week 10	50.0 (21.21)
Increase from Baseline at Week 12	353.3 (472.30)	6.7 (NA)
Increase from Baseline at Week 14	27.5 (8.24)
Increase from Baseline at Week 16	310.3 (460.00)	53.3 (NA)
Increase from Baseline at Week 24	244.2 (324.77)
Increase from Baseline at Week 32	121.9 (133.43)	10.0 (NA)
Increase from Baseline at Week 36	6.7 (NA)
Increase from Baseline at Week 40	246.3 (341.18)
Increase from Baseline at Week 48	248.8 (351.79)

16. Secondary Outcome

Title	E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Description	Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components.
Time Frame	Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat (mITT) population included all participants receiving at least one study treatment plus EP as assigned. Number analyzed is the number of participants with data available for analysis at a specified time-point.

Arm/Group Title	Cohort I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
HPV-16 ,Baseline	0.0 (0.00)	0.0 (0.00)
HPV-16, Week 2	2.5 (3.54)	0.0 (0.00)
HPV-16, Week 4	0.7 (1.60)	0.0 (0.00)
HPV-16, Week 6	2.5 (3.54)	0.0 (0.00)
HPV-16, Week 8	0.6 (1.48)	0.0 (0.00)
HPV-16, Week 10	0.0 (0.00)	0.00 (NA)
HPV-16, Week 12	0.8 (1.75)	0.0 (NA)
HPV-16, Week 14	2.0 (2.77)
HPV-16, Week 16	1.4 (2.44)	0.0 (NA)
HPV-16, Week 24	3.0 (2.36)	0.0 (NA)
HPV-16, Week 32	1.7 (2.59)	0.0 (NA)
HPV-16, Week 36	0.0 (0.00)	0.0 (NA)
HPV-16, Week 40	3.3 (2.89)
HPV-16, Week 48	3.7 (3.26)
HPV-18, Baseline	0.0 (0.00)	0.0 (0.00)
HPV-18, Week 2	3.1 (4.32)	0.0 (0.00)
HPV-18, Week 4	0.7 (1.60)	0.0 (0.00)
HPV-18, Week 6	0.0 (0.00)	0.0 (0.00)
HPV-18, Week 8	0.6 (1.48)	0.0 (0.00)
HPV-18, Week 10	1.3 (2.26)	0.0 (NA)
HPV-18, Week 12	0.8 (1.75)	6.1 (NA)
HPV-18, Week 14	0.0 (0.00)
HPV-18, Week 16	1.4 (2.53)	6.1 (NA)
HPV-18, Week 24	0.7 (1.60)	0.0 (NA)
HPV-18, Week 32	1.3 (2.02)	0.0 (NA)
HPV-18, Week 36	1.5 (3.05)	0.0 (NA)
HPV-18, Week 40	1.3 (2.26)
HPV-18, Week 48	0.0 (0.00)

17. Secondary Outcome

Title	E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA
Description	Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components.
Time Frame	Baseline and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 36, 40 and 48

Outcome Measure Data

Analysis Population Description

Modified intention-to-treat (mITT) population included all participants receiving at least one study treatment plus EP as assigned. Number analyzed is the number of participants with data available for analysis at a specified time-point.

Arm/Group Title	Cohort I: INO-3112: Curative Intent	Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.	Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
Measure Participants	7	3
HPV-16, Baseline	0.0 (0.00)	0.0 (0.00)
HPV-16, Week 2	0.0 (0.00)	2.0 (2.77)
HPV-16, Week 4	0.7 (1.60)	0.0 (0.00)
HPV-16, Week 6	0.0 (0.00)	0.0 (0.00)
HPV-16, Week 8	0.8 (2.05)	3.6 (5.10)
HPV-16, Week 10	3.3 (3.09)	7.2 (NA)
HPV-16, Week 12	2.0 (2.85)	7.2 (NA)
HPV-16, Week 14	3.1 (4.32)
HPV-16, Week 16	2.1 (2.75)	7.2 (NA)
HPV-16, Week 24	2.7 (3.13)	7.2 (NA)
HPV-16, Week 32	2.1 (2.38)	7.2 (NA)
HPV-16, Week 36	1.6 (2.14)	0.0 (NA)
HPV-16, Week 40	0.0 (0.00)
HPV-16, Week 48	0.0 (0.00)
HPV-18, Baseline	0.0 (0.00)	0.0 (0.00)
HPV-18, Week 2	1.7 (2.89)	0.0 (0.00)
HPV-18, Week 4	0.8 (2.05)	0.0 (0.00)
HPV-18, Week 6	5.0 (1.55)	0.0 (0.00)
HPV-18, Week 8	2.4 (3.72)	0.0 (0.00)
HPV-18, Week 10	1.3 (2.26)	0.0 (NA)
HPV-18, Week 12	2.2 (3.26)	7.2 (NA)
HPV-18, Week 14	2.0 (2.77)
HPV-18, Week 16	3.5 (3.56)	7.2 (NA)
HPV-18, Week 24	1.2 (2.94)	8.3 (NA)
HPV-18, Week 32	1.9 (3.05)	8.3 (NA)
HPV-18, Week 36	0.0 (0.00)	8.3 (NA)
HPV-18, Week 40	5.2 (4.51)
HPV-18, Week 48	3.6 (5.10)

Adverse Events

Time Frame	Up to 36 weeks
Arm/Group Title	Cohort I: INO-3112: Curative Intent		Cohort II: INO-3112: Salvage Therapy
Arm/Group Description	Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.		Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.
All Cause Mortality
	Cohort I: INO-3112: Curative Intent		Cohort II: INO-3112: Salvage Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		1/3 (33.3%)
Serious Adverse Events
	Cohort I: INO-3112: Curative Intent		Cohort II: INO-3112: Salvage Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/7 (42.9%)		2/3 (66.7%)
Blood and lymphatic system disorders
Disseminated Intravascular Coagulation	0/7 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Abdominal Pain	1/7 (14.3%)		0/3 (0%)
Intestinal Perforation	0/7 (0%)		1/3 (33.3%)
Infections and infestations
Endometritis	1/7 (14.3%)		0/3 (0%)
Pneumonia	1/7 (14.3%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Cohort I: INO-3112: Curative Intent		Cohort II: INO-3112: Salvage Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	0/7 (0%)		2/3 (66.7%)
Neutropenia	2/7 (28.6%)		0/3 (0%)
Cardiac disorders
Tachycardia	2/7 (28.6%)		1/3 (33.3%)
Ear and labyrinth disorders
Ear Pain	1/7 (14.3%)		0/3 (0%)
Gastrointestinal disorders
Abdominal Pain	1/7 (14.3%)		0/3 (0%)
Abdominal Pain Lower	1/7 (14.3%)		0/3 (0%)
Abdominal Pain Upper	1/7 (14.3%)		0/3 (0%)
Constipation	1/7 (14.3%)		0/3 (0%)
Defaecation Urgency	1/7 (14.3%)		0/3 (0%)
Diarrhoea	3/7 (42.9%)		0/3 (0%)
Dry Mouth	1/7 (14.3%)		0/3 (0%)
Gastrointestinal Motility Disorder	1/7 (14.3%)		1/3 (33.3%)
Gastrooesophageal Reflux Disease	2/7 (28.6%)		0/3 (0%)
Haemorrhoids	1/7 (14.3%)		0/3 (0%)
Hiatus Hernia	1/7 (14.3%)		0/3 (0%)
Large Intestine Polyp	2/7 (28.6%)		0/3 (0%)
Nausea	3/7 (42.9%)		1/3 (33.3%)
Rectal Ulcer	1/7 (14.3%)		0/3 (0%)
Toothache	1/7 (14.3%)		0/3 (0%)
Vomiting	1/7 (14.3%)		2/3 (66.7%)
General disorders
Chest Pain	1/7 (14.3%)		0/3 (0%)
Fatigue	2/7 (28.6%)		0/3 (0%)
Injection Site Bruising	2/7 (28.6%)		1/3 (33.3%)
Injection Site Discolouration	0/7 (0%)		1/3 (33.3%)
Injection Site Erythema	1/7 (14.3%)		0/3 (0%)
Injection Site Haemorrhage	1/7 (14.3%)		0/3 (0%)
Injection Site Pain	1/7 (14.3%)		2/3 (66.7%)
Injection Site Swelling	1/7 (14.3%)		1/3 (33.3%)
Malaise	1/7 (14.3%)		0/3 (0%)
Peripheral Swelling	0/7 (0%)		1/3 (33.3%)
Pyrexia	2/7 (28.6%)		1/3 (33.3%)
Hepatobiliary disorders
Cholecystitis	1/7 (14.3%)		0/3 (0%)
Hepatic Steatosis	1/7 (14.3%)		0/3 (0%)
Infections and infestations
Influenza	0/7 (0%)		1/3 (33.3%)
Pyometra	1/7 (14.3%)		0/3 (0%)
Sinusitis	0/7 (0%)		1/3 (33.3%)
Urinary Tract Infection	0/7 (0%)		1/3 (33.3%)
Injury, poisoning and procedural complications
Ligament Sprain	1/7 (14.3%)		0/3 (0%)
Radiation Proctopathy	0/7 (0%)		1/3 (33.3%)
Investigations
Weight Decreased	2/7 (28.6%)		0/3 (0%)
White Blood Cell Count Decreased	1/7 (14.3%)		0/3 (0%)
Metabolism and nutrition disorders
Decreased Appetite	2/7 (28.6%)		0/3 (0%)
Hyperglycaemia	1/7 (14.3%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/7 (28.6%)		1/3 (33.3%)
Back Pain	2/7 (28.6%)		0/3 (0%)
Bone Pain	1/7 (14.3%)		0/3 (0%)
Exostosis	0/7 (0%)		1/3 (33.3%)
Joint Swelling	1/7 (14.3%)		0/3 (0%)
Pain In Extremity	2/7 (28.6%)		1/3 (33.3%)
Pain In Jaw	1/7 (14.3%)		0/3 (0%)
Nervous system disorders
Dizziness	1/7 (14.3%)		1/3 (33.3%)
Dysgeusia	1/7 (14.3%)		0/3 (0%)
Headache	2/7 (28.6%)		0/3 (0%)
Neuropathy Peripheral	1/7 (14.3%)		0/3 (0%)
Paraesthesia	1/7 (14.3%)		0/3 (0%)
Parosmia	1/7 (14.3%)		0/3 (0%)
Psychiatric disorders
Anxiety	1/7 (14.3%)		1/3 (33.3%)
Insomnia	2/7 (28.6%)		1/3 (33.3%)
Renal and urinary disorders
Hydronephrosis	0/7 (0%)		1/3 (33.3%)
Nocturia	1/7 (14.3%)		0/3 (0%)
Pollakiuria	1/7 (14.3%)		0/3 (0%)
Proteinuria	1/7 (14.3%)		0/3 (0%)
Urge Incontinence	1/7 (14.3%)		0/3 (0%)
Urinary Incontinence	2/7 (28.6%)		0/3 (0%)
Reproductive system and breast disorders
Coital Bleeding	1/7 (14.3%)		0/3 (0%)
Dyspareunia	1/7 (14.3%)		0/3 (0%)
Uterine Pain	1/7 (14.3%)		0/3 (0%)
Uterine Prolapse	1/7 (14.3%)		0/3 (0%)
Vaginal Haemorrhage	2/7 (28.6%)		0/3 (0%)
Vaginal Stricture	0/7 (0%)		1/3 (33.3%)
Vulvovaginal Pain	1/7 (14.3%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/7 (14.3%)		0/3 (0%)
Dyspnoea	1/7 (14.3%)		1/3 (33.3%)
Dyspnoea Exertional	0/7 (0%)		1/3 (33.3%)
Oropharyngeal Pain	1/7 (14.3%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Excessive Granulation Tissue	1/7 (14.3%)		0/3 (0%)
Rash Maculo-Papular	1/7 (14.3%)		0/3 (0%)
Vascular disorders
Deep Vein Thrombosis	0/7 (0%)		1/3 (33.3%)
Hot Flush	2/7 (28.6%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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