Description:
This is a Phase I/IIa, open-label study to evaluate the safety, tolerability, and
immunogenicity of INO-3112 DNA vaccine delivered by electroporation (EP) to participants with
human papilloma virus (HPV) associated head and neck squamous cell cancer (HNSCC).
Title
- Brief Title: Study of HPV Specific Immunotherapy in Participants With HPV Associated Head and Neck Squamous Cell Carcinoma
- Official Title: Prospective Study of HPV Specific Immunotherapy in Subjects With HPV Associated Head and Neck Squamous Cell Carcinoma (HNSCCa)
Clinical Trial IDs
- ORG STUDY ID:
HPV-005
- NCT ID:
NCT02163057
Conditions
- Head and Neck Squamous Cell Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| INO-3112 | VGX-3100, INO-9012 | Cohort 1: Surgery Cohort |
Purpose
This is a Phase I/IIa, open-label study to evaluate the safety, tolerability, and
immunogenicity of INO-3112 DNA vaccine delivered by electroporation (EP) to participants with
human papilloma virus (HPV) associated head and neck squamous cell cancer (HNSCC).
Detailed Description
This is a Phase I/IIa, open-label, study to evaluate the safety, tolerability, and
immunogenicity of INO-3112 [6 mg of VGX-3100 (2 separate DNA plasmids respectively encoding
E6 and E7 proteins of HPV 16 and HPV 18) and 1 mg of INO-9012 (DNA plasmid encoding human
interleukin 12)] delivered by electroporation (EP) in up to 25 (twenty-five) participants
with HPV positive head and neck cancer. The immunotherapy was studied in the following two
groups of participants:
1. Participants who received immunotherapy before and after definitive surgery (Cohort I)
2. Participants who received immunotherapy at least 2 months after chemoradiation therapy
(Cohort II).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Cohort 1: Surgery Cohort | Other | Participants received up to two doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart before surgery and up to three doses of INO-3112 immunotherapy 3 weeks (± 3 days) apart after surgery for a total of no more than four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device. | |
| Cohort 2: Chemoradiation | Other | Participants received four doses of INO-3112 immunotherapy delivered IM followed by EP with CELLECTRA™-5P device 3 weeks (± 3 days) apart beginning approximately 2 to 6 months after chemoradiation therapy. | |
Eligibility Criteria
Inclusion Criteria:
1. Signed and dated written Ethics Committee approved informed consent.
2. Age ≥18 years.
3. Histologically confirmed HPV-positive (as assessed by p16 IHC or oncogenic HPV ISH or
PCR) mucosal squamous cell head and neck cancer:
- For pre-surgical participants, p16 positivity must be confirmed prior to the
first dose.
- For participants post-chemoradiation, HPV 16 and HPV 18 positivity must be
confirmed prior to the first dose.
4. Adequate bone marrow, hepatic, and renal function. ANC (Absolute Neutrophil Count) ≥
1.5x109 cell/ml, platelets ≥75,000 cells/mm3, hemoglobin ≥9.0 g/dL, concentrations of
total serum bilirubin within 1.5 x upper limit of normal (ULN), (Aspartate
Aminotransferase) AST, (Alanine Aminotransferase) ALT within 2.5x institutional ULN,
(Creatine Phosphokinase) CPK within 2.5 x ULN.
5. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
Exclusion Criteria:
1. Anticipated concomitant immunosuppressive therapy (excluding non-systemic inhaled,
topical skin and/or eye drop-containing corticosteroids).
2. Any concurrent condition requiring the continued use of systemic steroids (>10 mg
prednisone or equivalent per day) or the use of immunosuppressive agents. All other
corticosteroids must be discontinued at least 4 weeks prior to Day 0 of treatment.
3. Administration of any vaccine within 6 weeks of enrollment.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs) |
| Time Frame: | Up to 6 months post last dose |
| Safety Issue: | |
| Description: | An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product. TEAE is defined as any AE with onset after the administration of study medication through the end-of-study follow-up, or any event that was present at baseline but worsened in intensity or was subsequently considered treatment-related by the Investigator through the end of the study. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life-threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful or requires inpatient hospitalization or prolongation of existing hospitalization. |
Secondary Outcome Measures
| Measure: | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) |
| Time Frame: | Up to 6 months post last dose |
| Safety Issue: | |
| Description: | Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA. |
| Measure: | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA |
| Time Frame: | Up to 6 months post last dose |
| Safety Issue: | |
| Description: | Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA. |
| Measure: | Change From Baseline (CFB) in Combined HPV-16 and HPV-18 E6 and E7 Antigen-Specific Spot-Forming Units Per Million Peripheral Blood Mononuclear Cell (SFU/10^6 PBMC) as Assessed by Enzyme-Linked Immunosorbent Spot-Forming Assay (ELISpot) |
| Time Frame: | Baseline up to 6 months post last dose |
| Safety Issue: | |
| Description: | |
| Measure: | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry |
| Time Frame: | At baseline and Week 2 post last dose |
| Safety Issue: | |
| Description: | A flow cytometry assay called "lytic granule loading" was used to analyze CD8+ T cells specific for HPV-16 and CD8+ T cells specific for HPV-18 by evaluating the following markers: CD8, granzyme A (GrzA), granzyme B (GrzB), and perforin (Prf) co-expression with CD137, CD69, or CD38. |
| Measure: | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry |
| Time Frame: | At baseline and Week 2 post last dose |
| Safety Issue: | |
| Description: | A flow cytometry assay called "lytic granule loading" was used to analyze CD8+ T cells specific for HPV-16 and CD8+ T cells specific for HPV-18 by evaluating the following markers: CD8, granzyme A (GrzA), granzyme B (GrzB), and perforin (Prf) co-expression with CD137, CD69, or CD38. |
| Measure: | Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC) |
| Time Frame: | At screening and post-surgery |
| Safety Issue: | |
| Description: | The difference in means (post-surgery minus screening) for tumor-infiltrating lymphocytes (TILs) such as CD8, FoxP3, and perforin was analyzed using immunohistochemistry staining techniques. |
| Measure: | Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC) |
| Time Frame: | At screening and post-surgery |
| Safety Issue: | |
| Description: | The difference in means (post-surgery minus screening) for the CD8/FoxP3 ratio was analyzed using immunohistochemistry staining techniques. |
| Measure: | Phenotype of Cultured TILs |
| Time Frame: | Up to 6 months post last dose |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Inovio Pharmaceuticals |
Trial Keywords
- Head and neck squamous cell cancer
- Papillomavirus
Last Updated
January 22, 2021
