hTERT Immunotherapy Alone or in Combination With IL-12 DNA Followed by Electroporation in Adults With Solid Tumors at High Risk of Relapse

Study Overview
=================
Brief Summary
-----------------
This is a Phase I, open label study to evaluate the safety, tolerability, and immunogenicity of INO-1400 or INO-1401 alone or in combination with INO-9012, delivered by electroporation in subjects with high-risk solid tumor cancer with no evidence of disease after surgery and standard therapy. Subjects will be enrolled into one of ten treatment arms. Subjects will be assessed according to standard of care. Restaging and imaging studies will be performed to assess disease relapse per NCCN guidelines. RECIST will be used to validate the findings in cases of relapse.

Official Title
-----------------
A Multi-center Study of hTERT Immunotherapy Alone or in Combination With IL-12 DNA Followed by Electroporation in Adults With Solid Tumors at High Risk of Relapse Post Definitive Surgery and Standard Therapy

Conditions
-----------------
Breast Cancer, Lung Cancer, Pancreatic Cancer, Head and Neck Cancer, Ovarian Cancer, ColoRectal Cancer, Gastric Cancer, Esophageal Cancer, HepatoCellular Carcinoma

Intervention / Treatment
-----------------
* Biological: INO-1400
* Biological: INO-9012
* Biological: INO-1401


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Signed and dated written IRB approved informed consent; 2. Males or females aged ≥18 years; 3. Subjects with breast, lung or pancreatic carcinoma who are at high risk of relapse post definitive therapy at least 4 and no more than 24 weeks from completion of definitive therapy at the time of signing informed consent as described below for each indication: Breast carcinoma: Lung carcinoma: Pancreatic carcinoma: Head and neck squamous cell carcinoma: Ovarian cancer: Colorectal cancer Gastric and esophageal cancer Hepatocellular carcinoma Exclusion Criteria: 1. Previous treatment wth any TERT or IL-12 containing therapy, or any other DNA immunotherapy; 2. Any concurrent condition requiring the continued or anticipated use of systemic steroids (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids) or immunosuppressive therapy (excludes low dose methotrexate). All other systemic corticosteroids must be discontinued at least 4 weeks prior to first Study Treatment; 3. Administration of any vaccine within 4 weeks of the first study treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>2 mg INO-1400 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-1400<br> <br> * Other names: hTERT;|
| Experimental: Arm 2<br>8 mg INO-1400 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-1400<br> <br> * Other names: hTERT;|
| Experimental: Arm 3<br>2 mg INO-1400 + 0.5 mg INO-9012 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-1400<br> <br> * Other names: hTERT;Biological: INO-9012<br> <br> * Other names: IL-12;|
| Experimental: Arm 4<br>2 mg INO-1400 + 2 mg INO-9012 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-1400<br> <br> * Other names: hTERT;Biological: INO-9012<br> <br> * Other names: IL-12;|
| Experimental: Arm 5<br>8 mg INO-1400 + 0.5 mg INO-9012 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-1400<br> <br> * Other names: hTERT;Biological: INO-9012<br> <br> * Other names: IL-12;|
| Experimental: Arm 6<br>8 mg INO-1400 + 2 mg INO-9012 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-1400<br> <br> * Other names: hTERT;Biological: INO-9012<br> <br> * Other names: IL-12;|
| Experimental: Arm 7<br>2 mg INO-1401 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-1401<br> <br> * Other names: SynCon TERT;|
| Experimental: Arm 8<br>8 mg INO-1401 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-1401<br> <br> * Other names: SynCon TERT;|
| Experimental: Arm 9<br>8 mg INO-1401 + 0.5 mg INO-9012 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-9012<br> <br> * Other names: IL-12;Biological: INO-1401<br> <br> * Other names: SynCon TERT;|
| Experimental: Arm 10<br>8 mg INO-1401 + 2 mg INO-9012 delivered intramuscularly followed by electroporation at Day 0, Weeks 4, 8, and 12 | Biological: INO-9012<br> <br> * Other names: IL-12;Biological: INO-1401<br> <br> * Other names: SynCon TERT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE), NCI version 4.03 |  | Up to 2 years from first study treatment | 
| Injection site reactions including, but not necessarily limited to, local skin erythema, induration, pain and tenderness at administration site |  | Up to 14 weeks | 
| Changes in safety laboratory parameters |  | Up to 2 years from first study treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunotherapy, Human Telomerase Reverse Transcriptase (hTERT), Breast Neoplasms, Lung Neoplasms, Pancreatic Neoplasms, High Risk of Relapse, Post Definitive Surgery, Post Adjuvant Therapy, No Evidence of Disease