Inovio TRT-001: Telomerase DNA Immunotherapy in Breast, Lung, and Pancreatic Cancers

Inclusion Criteria:

1. Signed and dated written IRB approved informed consent;

2. Males or females aged ≥18 years;

3. Subjects with either breast, lung, pancreatic, head and neck, ovarian, colorectal,gastric, esophageal, or hepatocellular cancer who are at high risk of relapse postdefinitive surgery and standard therapy as described for each tumor type below: Breast carcinoma:

• Individuals with Stage III or Stage II/axillary node positive disease who arepost definitive surgery and at least 4 and no more than 24 weeks post completionof definitive chemotherapy and/or radiation adjuvant therapy at the time ofsigning informed consent (for ER+ or Her2+ positive subjects, these subjects maycontinue on hormonal therapy or anti-Her2 therapy as per standard of care);

• Individuals with Stage IV disease who have no evidence of disease after therapywhich includes a history of surgical resection of some or all tumor sites.

• Individuals with ER/PR/HER2 negative breast cancer (triple negative) of anystage who are status post definitive surgery but with residual microscopicbreast cancer in surgical specimen following adjuvant chemotherapy; if given;patient may be at least 4 and no more than 24 weeks from completion of adjuvanttherapy (e.g. radiation) at the time of signing informed consent;

• Individual receiving ongoing adjuvant endocrine (e.g. tamoxifen, anastrazole)therapy or trastuzumab is allowed. Squamous non-small cell Lung cancer:

• Individuals with Stage IB, II, or IIIA squamous non-small cell cancer who arestatus post definitive surgery; Individuals with Stage IV disease who have noevidence of disease after therapy which includes a history of surgical resection ofsome or all tumor types; Pancreatic carcinoma:

• Individuals with Stage I-III pancreatic ductal adenocarcinoma who are status postdefinitive surgery. Neuroendocrine tumors or tumors not of pancreatic origin are notallowed). Individuals with Stage IV disease who have no evidence of disease aftertherapy which includes a history of surgical resection of some or all tumor sites. Head and neck squamous cell carcinoma

• Individuals with Stage IV a/b head and neck squamous cell carcinoma who have noevidence of disease after therapy which includes a history of surgicalresection;

• Individuals with Stage III head and neck squamous cell carcinoma who are statuspost definitive therapy;

• Individuals with Stage IV a/b head and neck squamous cell carcinoma who have noevidence of disease after therapy which includes a history of surgicalresection. Ovarian cancer

• Individuals with ovarian fallopian tube, primary peritoneal carcinoma. Allowablehistologic types include high grade serous, high grade (grade 3- 3)endometrioid, carcinosarcoma, clear cell carcinoma, or mixed histology includingaforementioned types;

• Individuals with incompletely resected stage III or with stage IV disease whohave completed at least 6 but no more than 8 cycles of primary platinum-taxanebased chemotherapy and have undergone maximal attempt at cytoreductive surgery,either prior to chemotherapy or as an interval procedure;

• Individuals with Stage IV disease who have completed a platinum-taxanechemotherapy must be in complete remission based on no evidence of disease;

• Individuals treated with other agents (such as anti-angiogenic agents) as acomponent of primary therapy, either in combination with or followingplatinum-taxane chemotherapy, may be eligible as long as other eligibilitycriteria have been fulfilled. Colorectal cancer

• Individuals with Stage III histologically confirmed adenocarcinoma of colon orrectum who are status post definitive surgery;

• Individuals with Stage IV colorectal cancer (CRC) who have no evidence ofdisease after therapy which includes a history of surgical resection of some orall tumor sites. Gastric and esophageal cancer

• Individuals with Stage IIB, and III adenocarcinoma of the stomach, gastroesophagealjunction, or esophagus who are status post definitive surgery. Hepatocellular carcinoma

• Individuals with any stage of histologically proven hepatocellular carcinoma whoare status post definitive surgery;

• Individuals should not be suitable for liver transplant therapy or post livertransplantation;

• Individuals with no higher than Class A Child-Pugh;

4. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1;

5. Normal electrocardiogram (ECG) or ECG without clinically significant findings thatrequire clinical action;

6. Adequate organ function. At screening,

• Absolute neutrophil count (ANC) ≥ 1.5x103 cell/ml;

• Platelets ≥75,000 /ml (for HCC platelets ≥ 50,000/ml);

• Hemoglobin ≥ 9.0 g/dL;

• Serum creatinine < 2.0 mg/dL; For other blood and urine tests including bloodchemistry, hepatic and renal functions, test results should not be worse thanGrade 1 levels of abnormalities defined by CTCAE v4.03. For subjects who are atadvanced stages of disease (Stage III and above, in general), by theinvestigator's discretion and after consultation with medical monitor, testresults may not be worse than Grade 2 levels of abnormalities defined by CTCAEv4.03.

7. Subjects must agree that during the study, men cannot father children, and womencannot be or become pregnant if they are of child-bearing potential [(i.e., ≥ 12months of non-therapy-induced amenorrhea, confirmed by follicle stimulating hormone (FSH), if not on hormone replacement) or surgically sterile (vasectomy in males orabsence of ovaries and/or uterus in females)], agree to remain abstinent or use onehighly effective or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and at least through 12 weeks after the lastStudy Treatment dose. Abstinence is only acceptable if it is in line with thepreferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar,ovulation, symptothermal, or post-ovulation methods) and withdrawal are notacceptable methods of contraception. Examples of contraceptive methods with anexpected failure rate of < 1% per year include male sterilization and hormonalimplants. Alternatively, proper use of combined oral or injected hormonalcontraceptives and certain intrauterine devices (IUDs) or two methods (e.g., twobarrier methods such as a condom and a cervical cap) may be combined to achieve afailure rate of < 1% per year (barrier methods must always be supplemented with theuse of a spermicide);

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

Exclusion Criteria:

1. Previous treatment with any TERT or IL-12 containing therapy, or any immunotherapy;

2. Metastasis in brain or central nervous system;

3. Pregnant or breast-feeding subjects;

4. Allergic to any component of the investigational agents;

5. Recipient of an investigational therapy from another interventional clinical trialwithin 4 weeks of Study Treatment. Subjects can be enrolled if they are in anobservational study or within a long term follow up phase without any investigationaltherapy for at least 4 weeks prior to Study Treatment;

6. History of any clinically significant autoimmune disease or a transplant recipientwho is receiving chronic immunosuppression;

7. History of HIV infection or positive serological test for human immunodeficiencyvirus (HIV) at screening;

8. Any cardiac pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome;

9. Prior major surgery or radiation therapy within 4 weeks of Study Treatment;

10. Concurrent, long-term systemic corticosteroids (equivalent to prednisone > 10 mg/dayfor more than 2 weeks) or other systemic immunosuppressive therapy. Non-systemic,inhaled, topical skin, corticosteroid-containing eye drops and low dose methotrexateare allowed. Short-term use of corticosteroids in a chemotherapy regimen is allowed.All other systemic corticosteroids must be discontinued at least 4 weeks prior toStudy Treatment;

11. Recipient of any blood product within 2 weeks of Study Treatment;

12. Recipient of any vaccine within 4 weeks of Study Treatment;

13. Less than two acceptable sites exist for IM injection and EP between the use of bothdeltoids and lateral quadriceps muscles. A site for injection/EP is not acceptable ifthere are tattoos, keloids or hypertrophic scars within 2 cm of the injection/EPsite, or if there is implanted metal within the same limb. Any device implanted inthe chest (e.g., cardiac pacemaker, defibrillator or retained leads following deviceremoval) excludes the use of the deltoid muscle on the same side of the body;

14. Active use or dependence on illegal drug or alcohol that, in the opinion of theinvestigator, would interfere with adherence to study requirements and affectsubject's safety;

15. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) fortreatment of either a psychiatric or physical (i.e., infectious disease) illness;

16. Any medical and non-medical condition that, in the opinion of the investigator mayaffect the safety of the subject or the evaluation of study results.