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Safety and Efficacy of MEDI0457 and Durvalumab in Patients With HPV Associated Recurrent/Metastatic Head and Neck Cancer

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ClinicalTrials.gov Identifier: NCT03162224
Recruitment Status : Recruiting
First Posted : May 22, 2017
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

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 DNA vaccine in combination with durvalumab (also known as MEDI4736) which is a human monoclonal antibody directed against PD-L1, which blocks the interaction of PD-L1 with PD-1 and CD80.

An initial three to 12 patients (Safety Analysis Run-in patients) will be enrolled and assessed for safety before additional patients are enrolled.

The initial safety analysis run-in patients along with an approximate total of 50 patients with human papilloma virus associated recurrent or metastatic head and neck squamous cell cancer will be enrolled in this study and evaluated also for anti-tumor efficacy to MEDI0457 in combination with durvalumab.


Condition or disease Intervention/treatment Phase
Head and Neck Cancer Human Papilloma Virus Drug: MEDI0457 Device: CELLECTRA®5P device (CELLECTRA 2000) Drug: Durvalumab Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 26, 2017
Estimated Primary Completion Date : August 10, 2020
Estimated Study Completion Date : August 10, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: HPV associated recurrent/metastatic HNSCC
Approximately 50 patients with HPV associated recurrent/metastatic HNSCC
Drug: MEDI0457
MEDI0457 Administration by IM injection followed by electroporation (EP) using CELLECTRA®5P device.

Device: CELLECTRA®5P device (CELLECTRA 2000)
MEDI0457 Administration by IM injection followed by electroporation (EP) using CELLECTRA®5P device.

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




Primary Outcome Measures :
  1. Number of patients with changes in electrocariogram (ECG) from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab

  2. Occurrence of serious adverse events (SAEs) [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess by the occurrence of serious adverse events (SAEs)

  3. World Health organization (WHO)/ Eastern Cooperative Oncology Group Performace (ECOG) status [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess based on the following: fully active, restricted in physical activity, ambulatory and capable of self care, capable of limited self-care, completely disable.

  4. Concomitant medications [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess based on any accompanying or associated medication or procedure

  5. Number of patients with changes in laboratory parameters from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab

  6. Number of patients with changes in physical exam from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab

  7. Number of patients with changes in vital signs from baseline [ Time Frame: From time of informed consent and up to 28 days post end of treatment ]
    To assess the safety profile of MEDI0457 in combination with Durvalumab

  8. Occurrence of adverse events (AEs) [ Time Frame: From time of informed consent through 90 days post end of treatment ]
    To assess by the occurrence of adverse events (AEs)

  9. Objective response Rate (ORR) [ Time Frame: From time of first dose of study medication through 5 years ]
    To assess the antitumor activity of MEDI0457 plus Durvalumab in response-evaluable patients


Secondary Outcome Measures :
  1. Number of subjects who develop anti-drug antibodies [ Time Frame: From time of informed consent through 28 days post end of treatment ]
    To assess the immunogenicity of MEDI0457 and Durvalumab

  2. Objective Response Rate (ORR) [ Time Frame: From time of first dose of study medication through 5 years ]
    To assess the anti-tumor activity of MEDI0457 plus Durvalumab in as-treated patients

  3. Progression Free Survival (PFS) [ Time Frame: From time of first dose of study medication through 5 years ]
    To assess the anti-tumor activity of MEDI0457 plus Durvalumab

  4. Disease control Rate (16Weeks) [ Time Frame: From time of first dose of study medication through 5 years ]
    To assess anti-tumor activity in MEDI0457 plus Durvalumab

  5. Overall Survival (OS) [ Time Frame: From time of first dose of of study medication through 5 years ]
    To assess the anti-tumor activity of MEDI0457 plus Durvalumab

  6. Durva serum cTrough concentration for Pharmacokinetics [ Time Frame: From time of informed consent through 28 days post end of treatment ]
    To assess the pharmacokinetics of Durvalumab



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female subjects 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. Patients 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03162224


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
United States, Florida
Research Site Not yet recruiting
Orlando, Florida, United States, 32806
United States, Georgia
Research Site Recruiting
Atlanta, Georgia, United States, 30308
Research Site Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
Research Site Not yet recruiting
Chicago, Illinois, United States, 60612
United States, Indiana
Research Site Not yet recruiting
Indianapolis, Indiana, United States, 46202
United States, Kentucky
Research Site Not yet recruiting
Louisville, Kentucky, United States, 40202
United States, Maryland
Research Site Recruiting
Baltimore, Maryland, United States, 21287
United States, Michigan
Research Site Recruiting
Detroit, Michigan, United States, 48334
United States, Minnesota
Research Site Not yet recruiting
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Research Site Recruiting
Creve Coeur, Missouri, United States, 63141
Research Site Recruiting
Saint Louis, Missouri, United States, 63110
Research Site Withdrawn
Saint Louis, Missouri, United States, 63129
Research Site Withdrawn
Saint Peters, Missouri, United States, 63376
United States, New Jersey
Research Site Recruiting
Morristown, New Jersey, United States, 07960
Research Site Recruiting
Summit, New Jersey, United States, 07901
United States, New York
Research Site Recruiting
Bronx, New York, United States, 10461
United States, North Carolina
Research Site Recruiting
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Research Site Not yet recruiting
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: MedImmune LLC Study Director

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT03162224     History of Changes
Other Study ID Numbers: D8860C00005
First Posted: May 22, 2017    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by MedImmune LLC:
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

Additional relevant MeSH terms:
Head and Neck Neoplasms
Papilloma
Neoplasms by Site
Neoplasms
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs