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Head and Neck CancerPhase 1/2NCT03162224

Safety and Efficacy of MEDI0457 and Durvalumab in Participants With Human Papilloma Virus (HPV) Associated Recurrent/Metastatic Head and Neck Cancer

A Phase 1/2 study testing MEDI0457, CELLECTRA®5P device and Durvalumab in people with Head and Neck Cancer and Human Papilloma Virus, run by MedImmune LLC at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Head and Neck Cancer, Human Papilloma Virus
What is being tested?
MEDI0457, CELLECTRA®5P device and Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
14 sitesUnited States
Study dates
26 Jun 2017to 19 Mar 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female participants 18 years and older
  • 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.
  • Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
  • 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.

Who cannot join

  • Any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment Active or prior documented autoimmune disease with some exceptions.
  • 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.
  • 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).

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Research Site

    Atlanta, Georgia, 30308

  • Research Site

    Baltimore, Maryland, 21201

  • Research Site

    Baltimore, Maryland, 21287

  • Research Site

    Columbus, Ohio, 43210

  • Research Site

    Detroit, Michigan, 48201

  • Research Site

    Indianapolis, Indiana, 46202

  • Research Site

    Minneapolis, Minnesota, 55414

  • Research Site

    Morristown, New Jersey, 07960

  • Research Site

    Orlando, Florida, 32806

  • Research Site

    Philadelphia, Pennsylvania, 19104

  • Research Site

    San Francisco, California, 94115

  • Research Site

    St Louis, Missouri, 63110

  • Research Site

    The Bronx, New York, 10461

  • Research Site

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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.

Being tested
MEDI0457, CELLECTRA®5P device, Durvalumab
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
Medical subject headings
Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Oropharyngeal Neoplasms, Recurrence, Neoplasm Metastasis, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MEDI0457Drug

    Also called INO-3112

    MEDI0457 7 mg will be administered intramuscularly followed by electroporation (EP) using CELLECTRA®5P device.

  • CELLECTRA®5P deviceDevice

    Also called CELLECTRA 2000

    MEDI0457 7 mg will be administered intramuscularly followed by EP using CELLECTRA®5P device.

  • DurvalumabDrug

    Also called MEDI4736

    Durvalumab will be administered intravenously at a dose of 1500 mg every 4 weeks.

Study groups in NCT03162224
Study groupRoleWhat they receive
First-line Recurrent/Metastatic (1L R/M) Platinum Non-refractoryExperimentalParticipants with recurrent or metastatic disease and were non-refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then every 8 weeks (Q8W) and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then every 4 weeks (Q4W) until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
Receives: Drug: MEDI0457; Device: CELLECTRA®5P device; Drug: Durvalumab
1L R/M Platinum RefractoryExperimentalParticipants with R/M disease and were refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
Receives: Drug: MEDI0457; Device: CELLECTRA®5P device; Drug: Durvalumab
Second-line (2L) + R/MExperimentalParticipants with R/M disease and were treated with 1 or more lines of platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
Receives: Drug: MEDI0457; Device: CELLECTRA®5P device; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Day 1 through 90 days after the last dose of study drug (approximately 45 months)

  2. 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.

    Measured: Day 1 through 90 days after the last dose of study drug (approximately 45 months)

  3. Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs

    Participants with ECG abnormalities reported as TEAEs are reported.

    Measured: Day 1 through 90 days after the last dose of study drug (approximately 45 months)

  4. 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.

    Measured: Day 1 through 90 days after the last dose of study drug (approximately 45 months)

  5. 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.

    Measured: Day 1 through 90 days after the last dose of study drug (approximately 45 months)

  6. 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.

    Measured: Day 1 through 90 days after the last dose of study drug (approximately 45 months)

  7. 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.

    Measured: Day 1 through end of study (approximately 45 months)

Secondary outcomes (9)

  1. 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.

    Measured: Day 1 through end of study (approximately 45 months)

  2. 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.

    Measured: Day 1 through end of study (approximately 45 months)

  3. 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.

    Measured: Day 1 through end of study (approximately 45 months)

  4. Disease Control Rate (DCR) at Week 16 by RECIST Version 1.1 in Response-evaluable Population

    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.

    Measured: Week 16

  5. 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.

    Measured: Week 16

  6. 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.

    Measured: Day 1 through end of study (approximately 45 months)

  7. 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.

    Measured: Day 1 through end of study (approximately 45 months)

  8. 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.

    Measured: Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16

  9. Serum Concentrations of Durvalumab

    Serum concentrations of durvalumab is reported.

    Measured: Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2017
  2. Study start26 Jun 2017
  3. Primary completion19 Mar 2021
  4. Study completion19 Mar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03162224
Sponsor's protocol ID
D8860C00005
Status last verified
Aug 2022
First submitted
15 May 2017
Last updated
25 Aug 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MEDI0457, CELLECTRA®5P device and Durvalumab in people with Head and Neck Cancer and Human Papilloma Virus, run by MedImmune LLC at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) (time frame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03162224.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2022.

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