Clinical Trials /

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

NCT03162224

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: D8860C00005
  • NCT ID: NCT03162224

Conditions

  • Head and Neck Cancer
  • Human Papilloma Virus

Interventions

DrugSynonymsArms
MEDI0457HPV associated recurrent/metastatic HNSCC
DurvalumabHPV associated recurrent/metastatic HNSCC

Purpose

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 six to 12 patients (Safety Analysis patients) will be enrolled and assessed for safety before additional patients are enrolled. The initial safety analysis 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.

Trial Arms

NameTypeDescriptionInterventions
HPV associated recurrent/metastatic HNSCCExperimentalApproximately 50 patients with HPV associated recurrent/metastatic HNSCC
  • MEDI0457
  • Durvalumab

Eligibility 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).
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:To assess the safety profile of MEDI0457 in combination with Durvalumab

Secondary Outcome Measures

Measure:Number of subjects who develop anti-drug antibodies
Time Frame:From time of informed consent through 28 days post end of treatment
Safety Issue:
Description:To assess the immunogenicity of MEDI0457 and Durvalumab
Measure:Objective Response Rate (ORR)
Time Frame:From time First dose of study medication through 5 years
Safety Issue:
Description:To assess the anti-tumor activity of MEDI0457 plus Durvalumab in as-treated patients
Measure:Progression Free Survival (PFS)
Time Frame:From time First dose of study medication through 5 years
Safety Issue:
Description:To assess the anti-tumor activity of MEDI0457 plus Durvalumab
Measure:Disease control Rate (16Weeks)
Time Frame:From time First dose of study medication through 5 years
Safety Issue:
Description:To assess anti-tumor activity in MEDI0457 plus Durvalumab
Measure:Overall Survival (OS)
Time Frame:From time First dose of of study medication through 5 years
Safety Issue:
Description:To assess the anti-tumor activity of MEDI0457 plus Durvalumab
Measure:Durva serum cTrough concentration for Pharmacokinetics
Time Frame:From time of informed consent through 28 days post end of treatment
Safety Issue:
Description:To assess the pharmacokinetics of Durvalumab

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:MedImmune LLC

Trial 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

Last Updated

May 19, 2017