Brief Summary
This is a Phase 1b/2a, open-label, multi-center study to evaluate the safety and tolerability, anti-tumor activity, and immunogenicity of MEDI0457 (also known as INO 3112) a HPV Deoxyribonucleic Acid (DNA) vaccine in combination with durvalumab (also known as MEDI4736) which is a human monoclonal antibody directed against Programmed Death Ligand 1 (PD-L1), which blocks the interaction of PD-L1 with PD-1 and Cluster of differentiation 80 (CD80).
An initial three to 12 participants (Safety Analysis Run-in participants) will be enrolled and assessed for safety before additional participants are enrolled.
The initial safety analysis run-in participants along with an approximate total of 50 participants with human papilloma virus associated recurrent or metastatic head and neck squamous cell cancer (HNSCC) will be enrolled in this study and evaluated also for anti-tumor efficacy to MEDI0457 in combination with durvalumab.
An initial three to 12 participants (Safety Analysis Run-in participants) will be enrolled and assessed for safety before additional participants are enrolled.
The initial safety analysis run-in participants along with an approximate total of 50 participants with human papilloma virus associated recurrent or metastatic head and neck squamous cell cancer (HNSCC) will be enrolled in this study and evaluated also for anti-tumor efficacy to MEDI0457 in combination with durvalumab.
Brief Title
Safety and Efficacy of MEDI0457 and Durvalumab in Participants With Human Papilloma Virus (HPV) Associated Recurrent/Metastatic Head and Neck Cancer
Categories
Completion Date
Completion Date Type
Actual
Conditions
Head and Neck Cancer
Human Papilloma Virus
Eligibility Criteria
Inclusion Criteria:
1. Male and female participants 18 years and older
2. Histologically or cytologically confirmed diagnosis of HNSCC associated with HPV by a p16 immunohistochemistry (IHC) assay or HPV-16 or HPV-18 positive by nucleic acid testing.
3. Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
4. Participants who are platinum ineligible may be enrolled if they have received and failed an approved treatment and lack a treatment option with curative potential.
Exclusion criteria:
1. Any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment Active or prior documented autoimmune disease with some exceptions.
2. Current or prior use of immunosuppressive medication within 14 days prior to first study dose, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or equivalent. Steroids as premedication for hypersensitivity reactions due to radiographic contrast agents are allowed.
3. No prior exposure to immune-mediated therapy defined as prior exposure to T-cell and natural killer cell directed therapy (e.g., anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4, etc).
1. Male and female participants 18 years and older
2. Histologically or cytologically confirmed diagnosis of HNSCC associated with HPV by a p16 immunohistochemistry (IHC) assay or HPV-16 or HPV-18 positive by nucleic acid testing.
3. Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
4. Participants who are platinum ineligible may be enrolled if they have received and failed an approved treatment and lack a treatment option with curative potential.
Exclusion criteria:
1. Any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment Active or prior documented autoimmune disease with some exceptions.
2. Current or prior use of immunosuppressive medication within 14 days prior to first study dose, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or equivalent. Steroids as premedication for hypersensitivity reactions due to radiographic contrast agents are allowed.
3. No prior exposure to immune-mediated therapy defined as prior exposure to T-cell and natural killer cell directed therapy (e.g., anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4, etc).
Inclusion Criteria
Inclusion Criteria:
1. Male and female participants 18 years and older
2. Histologically or cytologically confirmed diagnosis of HNSCC associated with HPV by a p16 immunohistochemistry (IHC) assay or HPV-16 or HPV-18 positive by nucleic acid testing.
3. Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
4. Participants who are platinum ineligible may be enrolled if they have received and failed an approved treatment and lack a treatment option with curative potential.
1. Male and female participants 18 years and older
2. Histologically or cytologically confirmed diagnosis of HNSCC associated with HPV by a p16 immunohistochemistry (IHC) assay or HPV-16 or HPV-18 positive by nucleic acid testing.
3. Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
4. Participants who are platinum ineligible may be enrolled if they have received and failed an approved treatment and lack a treatment option with curative potential.
Gender
All
Gender Based
false
Keywords
Head and Neck Squamous Cell Carcinoma
Oropharyngeal Cancer
HPV
Human Papilloma Virus
Cancer Immunotherapy
Check point inhibitors
PD-L1 inhibitor
Recurrent or Metastatic Cancer
Durvalumab
MEDI0457
Antineoplastic agents
Neoplasms
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
99 Years
Minimum Age
18 Years
NCT Id
NCT03162224
Org Class
Industry
Org Full Name
MedImmune LLC
Org Study Id
D8860C00005
Overall Status
Completed
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1b/2a, Multi-Center Open-Label Study to Evaluate the Safety and Efficacy of Combination Treatment With MEDI0457 (INO-3112) and Durvalumab (MEDI4736) in Patients With Recurrent/Metastatic HPV Associated Head and Neck Squamous Cancer
Primary Outcomes
Outcome Description
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measures at the time of end of study.
Outcome Measure
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Outcome Time Frame
Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Outcome Description
Any laboratory abnormality during analysis of hematology, clinical chemistry, thyroid function tests, and urinalysis that was new in onset or worsened in severity or frequency from the baseline condition and required therapeutic intervention or diagnostic tests, led to discontinuation of study treatment, had accompanying or inducing symptoms or signs, or judged by the Investigator as clinically significant was recorded as AE. Participants with abnormal laboratory parameters reported as TEAEs are reported.
Outcome Measure
Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs
Outcome Time Frame
Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Outcome Description
Participants with ECG abnormalities reported as TEAEs are reported.
Outcome Measure
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
Outcome Time Frame
Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Outcome Description
Vital sign assessment included body temperature, respiration rate, pulse oximetry, blood pressure, heart rate, and weight. Participants with abnormal vital sign and/or abnormal physical examination reported as TEAEs are reported.
Outcome Measure
Number of Participants With Abnormal Vital Signs and/or Physical Examination Reported as TEAEs
Outcome Time Frame
Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Outcome Description
Participants who received concomitant medications which were ongoing at the start of treatment or started after the study treatment are included.
Outcome Measure
Number of Participants Who Received Any Concomitant Medications During the Study
Outcome Time Frame
Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Outcome Description
Participants with shift \>=3 changed from baseline in ECOG status are reported. ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. The scores are: 0 = Fully Active, able to carry out all pre-disease performance without restrictions; 1 = Restricted activity but ambulatory and able to carry out light work or work of a sedentary nature; 2 = Ambulatory and capable of self-care but unable to carry out work activities; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely Disabled, unable to carry out any self-care and totally confined to bed or chair; 5 = Dead.
Outcome Measure
Number of Participants With Shift >=3 Changed From Baseline in Eastern Cooperative Oncology Group Performance (ECOG) Status
Outcome Time Frame
Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Outcome Description
The objective response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. Percentage of participants with objective response is reported.
Outcome Measure
Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Response-evaluable Population
Outcome Time Frame
Day 1 through end of study (approximately 45 months)
Secondary Outcomes
Outcome Description
The objective response is defined as confirmed CR or confirmed PR based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. Percentage of participants with objective response is reported.
Outcome Time Frame
Day 1 through end of study (approximately 45 months)
Outcome Measure
Percentage of Participants With Objective Response by RECIST Version 1.1 in As-treated Population
Outcome Description
The objective response is defined as confirmed CR or confirmed PR based on irRECIST v1.1 guidelines. The irCR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The irPR is defined as \>= 50% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed irCR or irPR is defined as 2 irCRs or 2 irPRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. Percentage of participants with objective response is reported.
Outcome Time Frame
Day 1 through end of study (approximately 45 months)
Outcome Measure
Percentage of Participants With Objective Response by Immune-related RECIST (irRECIST) in Response-evaluable Population
Outcome Description
The objective response is defined as confirmed CR or confirmed PR based on irRECIST v1.1 guidelines. The irCR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The irPR is defined as \>= 50% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed irCR or irPR is defined as 2 irCRs or 2 irPRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. Percentage of participants with objective response is reported.
Outcome Time Frame
Day 1 through end of study (approximately 45 months)
Outcome Measure
Percentage of Participants With Objective Response by irRECIST in As-treated Population
Outcome Description
The DCR is defined percentage of participants with CR, PR, or stable disease (SD) at 16 weeks based on RECIST v1.1 guidelines. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A PR is defined as \>= 30% decrease in the sum of longest diameters of target lesions compared to baseline and no new non-target lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum longest diameter since the study treatment started, and persistence of one or more non-target lesion(s) or / and maintenance of tumor marker level above the normal limits.
Outcome Time Frame
Week 16
Outcome Measure
Disease Control Rate (DCR) at Week 16 by RECIST Version 1.1 in Response-evaluable Population
Outcome Description
The DCR is defined percentage of participants with CR, PR, or SD at 16 weeks based on RECIST v1.1 guidelines. A CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. A PR is defined as \>= 30% decrease in the sum of longest diameters of target lesions compared to baseline and no new non-target lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum longest diameter since the study treatment started, and persistence of one or more non-target lesion(s) or / and maintenance of tumor marker level above the normal limits.
Outcome Time Frame
Week 16
Outcome Measure
DCR at Week 16 by RECIST Version 1.1 in As-treated Population
Outcome Description
The PFS is defined as the time from the date of start of study treatment until the documentation of disease progression based on RECIST version 1.1 or death due to any cause, whichever occurs first. The progressive disease is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. Participants who were not progressed or died at the time of the analysis were censored at the time of the latest date of assessment from their last evaluable RECIST version 1.1 assessment. The PFS was estimated using Kaplan-Meier method.
Outcome Time Frame
Day 1 through end of study (approximately 45 months)
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
Overall survival is defined as the time from the date of start of study treatment until death due to any cause. Any participant not died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The OS was estimated using Kaplan-Meier method.
Outcome Time Frame
Day 1 through end of study (approximately 45 months)
Outcome Measure
Overall Survival (OS)
Outcome Description
Number of participants with positive ADA titer to durvalumab are reported. ADA prevalence is defined as ADA positive at any point (baseline and post-baseline); persistent positive is defined as ADA positive at Week 16, and transient positive is defined as positive at Week 8 but not at Week 16, regardless of baseline positivity.
Outcome Time Frame
Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16
Outcome Measure
Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab
Outcome Description
Serum concentrations of durvalumab is reported.
Outcome Time Frame
Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16
Outcome Measure
Serum Concentrations of Durvalumab
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
99
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone