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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
35
MEDI0457 7 mg will be administered intramuscularly followed by electroporation (EP) using CELLECTRA®5P device.
MEDI0457 7 mg will be administered intramuscularly followed by EP using CELLECTRA®5P device.
Durvalumab will be administered intravenously at a dose of 1500 mg every 4 weeks.
Research Site
San Francisco, California, United States
Research Site
Orlando, Florida, United States
Research Site
Atlanta, Georgia, United States
Research Site
Indianapolis, Indiana, United States
Research Site
Baltimore, Maryland, United States
Research Site
Baltimore, Maryland, United States
Research Site
Detroit, Michigan, United States
Research Site
Minneapolis, Minnesota, United States
Research Site
St Louis, Missouri, United States
Research Site
Morristown, New Jersey, United States
...and 4 more locations
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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.
Time frame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs
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.
Time frame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
Participants with ECG abnormalities reported as TEAEs are reported.
Time frame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Number of Participants With Abnormal Vital Signs and/or Physical Examination Reported as TEAEs
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.
Time frame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Number of Participants Who Received Any Concomitant Medications During the Study
Participants who received concomitant medications which were ongoing at the start of treatment or started after the study treatment are included.
Time frame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Number of Participants With Shift >=3 Changed From Baseline in Eastern Cooperative Oncology Group Performance (ECOG) Status
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.
Time frame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Response-evaluable Population
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.
Time frame: Day 1 through end of study (approximately 45 months)
Percentage of Participants With Objective Response by RECIST Version 1.1 in As-treated Population
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.
Time frame: Day 1 through end of study (approximately 45 months)
Percentage of Participants With Objective Response by Immune-related RECIST (irRECIST) in Response-evaluable Population
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.
Time frame: Day 1 through end of study (approximately 45 months)
Percentage of Participants With Objective Response by irRECIST in As-treated Population
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.
Time frame: Day 1 through end of study (approximately 45 months)
Disease Control Rate (DCR) at Week 16 by RECIST Version 1.1 in Response-evaluable Population
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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.
Time frame: Week 16
DCR at Week 16 by RECIST Version 1.1 in As-treated Population
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.
Time frame: Week 16
Progression Free Survival (PFS)
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.
Time frame: Day 1 through end of study (approximately 45 months)
Overall Survival (OS)
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.
Time frame: Day 1 through end of study (approximately 45 months)
Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab
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.
Time frame: Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16
Serum Concentrations of Durvalumab
Serum concentrations of durvalumab is reported.
Time frame: Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16