Patient case: 45-year-old female with cervical cancer; genetic feature: ERBB2 (S310Y)

Clinical trial: A Study of INO-3112 DNA Vaccine With Electroporation in Patients With Cervical Cancer

Summary: This is an open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 DNA vaccines delivered by Electroporation to female subjects with HPV-16 and/or 18-positive cervical carcinoma.

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 subjects 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 1) or in subjects with persistent and/or recurrent cervical cancer associated with HPV 16 and/or 18 following salvage therapy (Cohort 2).

Eligibility: 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 meeting 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
  o 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
  o No CNS/spinal metastases
  -  Able to initiate study treatment at least 2 weeks but no more than 4 weeks after completion of salvage therapy
  -  Subject has a life expectancy of at least 12 months as assessed by the investigator
  4. 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 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 subject 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; subject must have had an serologic test performed within 12 months of informed consent);
  5. Prior major surgery from which the subject 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;
  n) Active drug or alcohol use or dependence; o) Imprisonment or compulsory detainment for treatment of either a psychiatric or physical (i.e. infectious disease) illness; p) History of immunosuppressive or autoimmune disease; q) Any other illnesses or conditions that in the opinion of the investigator may affect the safety of the subject or limit the evaluation of a subject or any study endpoint.

Relevance to patient case: not relevant