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

Inovio Pharmaceuticals10 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cervical Cancer

Interventions

INO-3112BIOLOGICAL

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.

CELLECTRA™-5PDEVICE

CELLECTRA™-5P was used for EP following IM delivery of INO-3112 on Day 0, Week 4, Week 8, and Week 12.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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. 1. 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 2. 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 4. Electrocardiogram (ECG) with no clinically significant findings. 5. Chemistry, liver function tests, renal function, total CPK and hematology lab results must be ≤ Grade 1 at the time of screening. 6. Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 1. 7. Adequate venous access for repeated blood sampling according to the study schedule. 8. 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 \[IUD\]). 9. 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.

Locations (3)

University of Chicago Medical Center

Chicago, Illinois, United States

University of Michigan

Ann Arbor, Michigan, United States

Columbia University Medical Center

New York, New York, United States

Outcomes

Primary Outcomes

Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)

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

Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03)

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

Percentage of Participants With Injection Site Reactions

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.

Data from ClinicalTrials.gov

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