Head and Neck Squamous Cell Cancer
Conditions
Keywords
Head and neck squamous cell cancer, Papillomavirus
Brief summary
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).
Interventions
BIOLOGICALINO-3112
1.1 mL of INO-3112 (VGX-3100 + INO-9012) delivered intramuscularly (IM) followed immediately by electroporation (EP) with CELLECTRA™-5P device for a total of 4 doses of immunotherapy.
DEVICECELLECTRA™-5P
CELLECTRA™-5P device was used for EP following IM delivery of INO-3112 for a total of 4 doses of immunotherapy.
Sponsors
University of Pennsylvania
Inovio Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs) | Up to 6 months post last dose | 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
| Measure | Time frame | Description |
|---|---|---|
| E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | Up to 6 months post last dose | Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA. |
| E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | Up to 6 months post last dose | Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA. |
| 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) | Baseline up to 6 months post last dose | — |
| Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | At baseline and Week 2 post last dose | 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. |
| Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC) | At screening and post-surgery | 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. |
| Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC) | At screening and post-surgery | The difference in means (post-surgery minus screening) for the CD8/FoxP3 ratio was analyzed using immunohistochemistry staining techniques. |
| Phenotype of Cultured TILs | Up to 6 months post last dose | — |
| Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | At baseline and Week 2 post last dose | 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. |
Countries
United States
Participant flow
Recruitment details
Participants with a diagnosis of HPV associated head and neck squamous cell carcinoma were enrolled in the study between 13th August 2014 to 23rd January 2017.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Surgery Cohort 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. | 6 |
| Cohort 2: Chemoradiation 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. | 16 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Participant Refusal to Continue | 2 | 2 |
| Overall Study | Participant Significant Noncompliance | 0 | 1 |
| Overall Study | Progression of Disease | 1 | 2 |
Baseline characteristics
| Characteristic | Cohort 2: Chemoradiation | Total | Cohort 1: Surgery Cohort |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 10.26 | 57.3 years STANDARD_DEVIATION 9.43 | 62.2 years STANDARD_DEVIATION 4.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 22 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 19 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 14 Participants | 20 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 16 |
| other Total, other adverse events | 6 / 6 | 15 / 16 |
| serious Total, serious adverse events | 2 / 6 | 0 / 16 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs)
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.
Time frame: Up to 6 months post last dose
Population: Safety population included all participants who received at least one dose of study treatment plus EP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Surgery Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs) | At least 1 TEAE | 6 Participants |
| Cohort 1: Surgery Cohort | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs) | At least 1 Treatment-emergent SAE | 2 Participants |
| Cohort 2: Chemoradiation | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs) | At least 1 TEAE | 15 Participants |
| Cohort 2: Chemoradiation | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Event (SAEs) | At least 1 Treatment-emergent SAE | 0 Participants |
Secondary
Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry
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.
Time frame: At baseline and Week 2 post last dose
Population: ANoD population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD137+GrzA+GrzB+Prf+, baseline | 0.09 cells/million T-cells | Standard Deviation 0.124 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD137+GrzA+GrzB+Prf+,CFB Week 2 post last dose | 0.16 cells/million T-cells | Standard Deviation 0.23 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD69+GrzA+GrzB+Prf+, baseline | 0.00 cells/million T-cells | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD69+GrzA+GrzB+Prf+, CFB Week 2 post last dose | 0.48 cells/million T-cells | Standard Deviation 0.282 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD38+GrzA+GrzB+Prf+, baseline | 0.00 cells/million T-cells | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD38+GrzA+GrzB+Prf+, CFB Week 2 post last dose | 0.89 cells/million T-cells | Standard Deviation 0.457 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD38+GrzA+GrzB+Prf+, baseline | 0.14 cells/million T-cells | Standard Deviation 0.163 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD137+GrzA+GrzB+Prf+, baseline | 0.02 cells/million T-cells | Standard Deviation 0.039 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD69+GrzA+GrzB+Prf+, CFB Week 2 post last dose | 0.20 cells/million T-cells | Standard Deviation 0.471 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD137+GrzA+GrzB+Prf+,CFB Week 2 post last dose | 0.11 cells/million T-cells | Standard Deviation 0.188 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD38+GrzA+GrzB+Prf+, CFB Week 2 post last dose | 0.26 cells/million T-cells | Standard Deviation 0.555 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-16 as Assessed by Flow Cytometry | CD8+CD69+GrzA+GrzB+Prf+, baseline | 0.17 cells/million T-cells | Standard Deviation 0.345 |
Secondary
Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry
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.
Time frame: At baseline and Week 2 post last dose
Population: ANoD population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD137+GrzA+GrzB+Prf+, baseline | 0.00 cells/million T-cells | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD137+GrzA+GrzB+Prf+,CFB Week 2 post last dose | 0.09 cells/million T-cells | Standard Deviation 0.073 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD69+GrzA+GrzB+Prf+, baseline | 0.00 cells/million T-cells | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD69+GrzA+GrzB+Prf+, CFB Week 2 post last dose | 0.20 cells/million T-cells | Standard Deviation 0.283 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD38+GrzA+GrzB+Prf+, baseline | 0.00 cells/million T-cells | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD38+GrzA+GrzB+Prf+, CFB Week 2 post last dose | 0.73 cells/million T-cells | Standard Deviation 0.841 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD38+GrzA+GrzB+Prf+, baseline | 0.06 cells/million T-cells | Standard Deviation 0.135 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD137+GrzA+GrzB+Prf+, baseline | 0.05 cells/million T-cells | Standard Deviation 0.07 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD69+GrzA+GrzB+Prf+, CFB Week 2 post last dose | 0.34 cells/million T-cells | Standard Deviation 0.54 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD137+GrzA+GrzB+Prf+,CFB Week 2 post last dose | 0.07 cells/million T-cells | Standard Deviation 0.089 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD38+GrzA+GrzB+Prf+, CFB Week 2 post last dose | 0.36 cells/million T-cells | Standard Deviation 0.552 |
| Cohort 2: Chemoradiation | Change From Baseline (CFB) in CD8+ T-Cell Responses Specific for HPV-18 as Assessed by Flow Cytometry | CD8+CD69+GrzA+GrzB+Prf+, baseline | 0.10 cells/million T-cells | Standard Deviation 0.158 |
Secondary
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
Population: ANoD population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Surgery Cohort | 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) | Baseline | 20.3 SFU/10^6 PBMC | Standard Deviation 22.65 |
| Cohort 1: Surgery Cohort | 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) | CFB at 2nd dose | 24.2 SFU/10^6 PBMC | Standard Deviation 34.56 |
| Cohort 1: Surgery Cohort | 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) | CFB at 3rd dose | 15.0 SFU/10^6 PBMC | Standard Deviation 17.54 |
| Cohort 1: Surgery Cohort | 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) | CFB at 4th dose | 50.3 SFU/10^6 PBMC | Standard Deviation 49.06 |
| Cohort 1: Surgery Cohort | 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) | CFB at Week 2 post last dose | 68.3 SFU/10^6 PBMC | Standard Deviation 63.98 |
| Cohort 1: Surgery Cohort | 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) | CFB at 1st long term follow-up | 182.2 SFU/10^6 PBMC | Standard Deviation 211.31 |
| Cohort 1: Surgery Cohort | 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) | CFB at 2nd long term follow-up | 102.3 SFU/10^6 PBMC | Standard Deviation 140.03 |
| Cohort 1: Surgery Cohort | 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) | CFB at 3rd long term follow-up | 127.6 SFU/10^6 PBMC | Standard Deviation 3.46 |
| Cohort 1: Surgery Cohort | 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) | CFB at 4th long term follow-up | 41.4 SFU/10^6 PBMC | — |
| Cohort 1: Surgery Cohort | 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) | CFB at 5th long term follow-up | 129.1 SFU/10^6 PBMC | Standard Deviation 19.87 |
| Cohort 1: Surgery Cohort | 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) | CFB at 6th long term follow-up | 141.7 SFU/10^6 PBMC | — |
| Cohort 1: Surgery Cohort | 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) | CFB at follow-up Week 2 post-surgery | 154.2 SFU/10^6 PBMC | Standard Deviation 168.5 |
| Cohort 1: Surgery Cohort | 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) | CFB at end of study follow-up | 50.0 SFU/10^6 PBMC | Standard Deviation 42.75 |
| Cohort 2: Chemoradiation | 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) | Baseline | 11.7 SFU/10^6 PBMC | Standard Deviation 10.25 |
| Cohort 2: Chemoradiation | 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) | CFB at 2nd long term follow-up | 151.1 SFU/10^6 PBMC | Standard Deviation 94.32 |
| Cohort 2: Chemoradiation | 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) | CFB at 2nd dose | 96.9 SFU/10^6 PBMC | Standard Deviation 118.41 |
| Cohort 2: Chemoradiation | 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) | CFB at 5th long term follow-up | 0.0 SFU/10^6 PBMC | — |
| Cohort 2: Chemoradiation | 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) | CFB at 3rd dose | 158.9 SFU/10^6 PBMC | Standard Deviation 231.73 |
| Cohort 2: Chemoradiation | 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) | CFB at 3rd long term follow-up | 113.2 SFU/10^6 PBMC | Standard Deviation 153.59 |
| Cohort 2: Chemoradiation | 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) | CFB at 4th dose | 263.6 SFU/10^6 PBMC | Standard Deviation 597.8 |
| Cohort 2: Chemoradiation | 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) | CFB at end of study follow-up | 70.5 SFU/10^6 PBMC | Standard Deviation 87.09 |
| Cohort 2: Chemoradiation | 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) | CFB at Week 2 post last dose | 354.7 SFU/10^6 PBMC | Standard Deviation 632.29 |
| Cohort 2: Chemoradiation | 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) | CFB at 4th long term follow-up | 29.8 SFU/10^6 PBMC | Standard Deviation 28.11 |
| Cohort 2: Chemoradiation | 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) | CFB at 1st long term follow-up | 128.8 SFU/10^6 PBMC | Standard Deviation 132.05 |
| Cohort 2: Chemoradiation | 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) | CFB at 6th long term follow-up | 11.7 SFU/10^6 PBMC | — |
Secondary
E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.
Time frame: Up to 6 months post last dose
Population: Assigned Number of Doses (ANoD) population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 1st long term follow-up | 1.3 log titer | Standard Deviation 2.51 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 2nd dose | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, surgery | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 3rd dose | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 2nd long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 4th dose | 1.0 log titer | Standard Deviation 2.24 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 3rd dose | 2.6 log titer | Standard Deviation 2.39 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 1st long term follow-up | 1.3 log titer | Standard Deviation 2.51 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 3rd long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 2nd long term follow-up | 1.0 log titer | Standard Deviation 2.24 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 1st dose | 3.6 log titer | Standard Deviation 4.53 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 3rd long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 4th long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 4th long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 4th dose | 2.4 log titer | Standard Deviation 3.44 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 5th long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 5th long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, Week 2 post last dose | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, initial surgery | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, follow-up Week 2 post-surgery | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, optional surgery | 0.0 log titer | — |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, unscheduled visit | 0.0 log titer | — |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, end of study follow-up | 1.5 log titer | Standard Deviation 3.05 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, Week 2 post last dose | 2.8 log titer | Standard Deviation 3.48 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, initial surgery | 1.0 log titer | Standard Deviation 2.24 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, surgery | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, follow-up Week 2 post-surgery | 4.6 log titer | Standard Deviation 1.27 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, optional surgery | 0.0 log titer | — |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, unscheduled visit | 3.9 log titer | — |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, end of study follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 2nd dose | 2.2 log titer | Standard Deviation 2.61 |
| Cohort 1: Surgery Cohort | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 1st dose | 0.0 log titer | Standard Deviation 0 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, end of study follow-up | 2.8 log titer | Standard Deviation 3.01 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 1st dose | 0.4 log titer | Standard Deviation 1.18 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 2nd dose | 0.0 log titer | Standard Deviation 0 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 3rd dose | 1.2 log titer | Standard Deviation 2.33 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 4th dose | 1.0 log titer | Standard Deviation 2.42 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, Week 2 post last dose | 2.3 log titer | Standard Deviation 2.91 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 1st long term follow-up | 1.0 log titer | Standard Deviation 2.42 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 2nd long term follow-up | 1.2 log titer | Standard Deviation 2.63 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 3rd long term follow-up | 0.8 log titer | Standard Deviation 2.4 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 4th long term follow-up | 1.4 log titer | Standard Deviation 3.39 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 5th long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, 6th long term follow-up | 3.1 log titer | Standard Deviation 4.32 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ELISA titer, end of study follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 1st dose | 0.4 log titer | Standard Deviation 1.18 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 2nd dose | 0.7 log titer | Standard Deviation 1.69 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 3rd dose | 0.8 log titer | Standard Deviation 1.88 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, Week 2 post last dose | 3.0 log titer | Standard Deviation 3.25 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 1st long term follow-up | 2.0 log titer | Standard Deviation 3.04 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 2nd long term follow-up | 1.3 log titer | Standard Deviation 2.09 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 3rd long term follow-up | 1.1 log titer | Standard Deviation 2.28 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 4th long term follow-up | 1.7 log titer | Standard Deviation 2.68 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 5th long term follow-up | 1.7 log titer | Standard Deviation 2.89 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 6th long term follow-up | 6.1 log titer | Standard Deviation 0 |
| Cohort 2: Chemoradiation | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18 ELISA titer, 4th dose | 1.2 log titer | Standard Deviation 2.12 |
Secondary
E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA
Titers for HPV-16 and HPV-18 E6- and E7-specific antibodies were assessed by ELISA.
Time frame: Up to 6 months post last dose
Population: ANoD population included all participants who received their assigned number of doses of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 3rd dose | 1.2 log titer | Standard Deviation 2.73 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 2nd dose | 2.5 log titer | Standard Deviation 2.89 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 2nd long term follow-up | 0.8 log titer | Standard Deviation 1.75 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 3rd dose | 2.7 log titer | Standard Deviation 3.67 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, initial surgery | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 4th dose | 4.5 log titer | Standard Deviation 4.17 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 3rd long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, Week 2 post last dose | 8.0 log titer | Standard Deviation 1.65 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 4th dose | 3.0 log titer | Standard Deviation 3.06 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 1st long term follow-up | 6.9 log titer | Standard Deviation 2.44 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 4th long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 2nd long term follow-up | 5.8 log titer | Standard Deviation 3.98 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 2nd dose | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 3rd long term follow-up | 2.0 log titer | Standard Deviation 2.77 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 5th long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 4th long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, Week 2 post last dose | 2.8 log titer | Standard Deviation 3.48 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 5th long term follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, surgery | 2.4 log titer | Standard Deviation 4.7 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, follow-up Week 2 post-surgery | 1.3 log titer | Standard Deviation 2.26 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, optional surgery | 0.0 log titer | — |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, unscheduled visit | 0.0 log titer | — |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, end of study follow-up | 4.4 log titer | Standard Deviation 5.29 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, 1st dose | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, initial surgery | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, surgery | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, follow-up Week 2 post-surgery | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, optional surgery | 0.0 log titer | — |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, unscheduled visit | 0.0 log titer | — |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, end of study follow-up | 0.0 log titer | Standard Deviation 0 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 1st long term follow-up | 2.5 log titer | Standard Deviation 3.03 |
| Cohort 1: Surgery Cohort | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 1st dose | 0.0 log titer | Standard Deviation 0 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, end of study follow-up | 4.6 log titer | Standard Deviation 3.03 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 6th long term follow-up | 8.3 log titer | Standard Deviation 0 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, 1st dose | 0.4 log titer | Standard Deviation 1.18 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 2nd dose | 0.5 log titer | Standard Deviation 1.69 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 3rd dose | 2.1 log titer | Standard Deviation 2.85 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 4th dose | 3.0 log titer | Standard Deviation 3.41 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, Week 2 post last dose | 3.3 log titer | Standard Deviation 4.09 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 1st long term follow-up | 2.8 log titer | Standard Deviation 3.63 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 2nd long term follow-up | 1.6 log titer | Standard Deviation 3.28 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 3rd long term follow-up | 1.5 log titer | Standard Deviation 3.24 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 4th long term follow-up | 0.8 log titer | Standard Deviation 2.05 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 5th long term follow-up | 3.1 log titer | Standard Deviation 5.43 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, 6th long term follow-up | 4.2 log titer | Standard Deviation 5.87 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16 ELISA titer, end of study follow-up | 1.3 log titer | Standard Deviation 2.45 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 1st dose | 0.5 log titer | Standard Deviation 1.51 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 2nd dose | 0.3 log titer | Standard Deviation 1.08 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 3rd dose | 1.3 log titer | Standard Deviation 2.03 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 4th dose | 3.0 log titer | Standard Deviation 3.21 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, Week 2 post last dose | 4.2 log titer | Standard Deviation 2.83 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 1st long term follow-up | 4.5 log titer | Standard Deviation 3.41 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 2nd long term follow-up | 1.8 log titer | Standard Deviation 3.13 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 3rd long term follow-up | 3.1 log titer | Standard Deviation 3.79 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 4th long term follow-up | 2.5 log titer | Standard Deviation 2.83 |
| Cohort 2: Chemoradiation | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18 ELISA titer, 5th long term follow-up | 5.5 log titer | Standard Deviation 4.8 |
Secondary
Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
The difference in means (post-surgery minus screening) for the CD8/FoxP3 ratio was analyzed using immunohistochemistry staining techniques.
Time frame: At screening and post-surgery
Population: ANoD population included all participants who received their assigned number of doses of study treatment plus EP.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: Surgery Cohort | Mean Difference in CD8/FoxP3 Ratio in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC) | 0.2 ratio |
Secondary
Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC)
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.
Time frame: At screening and post-surgery
Population: ANoD population included all participants who received their assigned number of doses of study treatment plus EP.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1: Surgery Cohort | Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC) | CD8 | 268.5 positive cells per square millimeter |
| Cohort 1: Surgery Cohort | Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC) | FoxP3 | -79.8 positive cells per square millimeter |
| Cohort 1: Surgery Cohort | Mean Difference in Tumor Infiltrating Lymphocytes (TILs) in Presurgical and Surgical Tumor Tissue Samples of Cohort I as Assessed by Immunohistochemistry (IHC) | Perforin | 9.5 positive cells per square millimeter |
Secondary
Phenotype of Cultured TILs
Time frame: Up to 6 months post last dose
Population: Data was not collected due to lack of recoverable samples sufficient for analysis