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This is a Trial of MG1-E6E7 With Ad-E6E7 and Atezolizumab in Patients With HPV Associated Cancers

NCT03618953

Description:

This is a Phase 1/1b open-label dose escalation trial of Ad/MG1-E6E7 and sequential treatment with atezolizumab in patients with HPV associated cancers. This study will consist of two arms. Both arms will dose escalate (MG1-E6E7) using a 3 + 3 design in Phase 1 to establish initial safety and the maximum tolerated dose (MTD) / maximum feasible dose (MFD). - Arm 1 - intravenous (IV) administration of MG1-E6E7 following intramuscular (IM) AD-E6E7 priming and subsequent treatment with IV atezolizumab. - Arm 2 - intratumoral (IT) and IV injection of MG1-E6E7 following (IM) Ad-E6E7 priming and subsequent treatment with IV atezolizumab. In the Phase 1b expansion for each arm, additional patients will be enrolled at the MTD as determined in Phase 1 in order to more thoroughly explore immune response, pharmacokinetics/dynamics, and safety for the patient populations with Cervical cancer, HPV positive (HPV+) Oropharyngeal cancer (Phase 1B, Arm 1, Cohorts A and B respectively) and HPV+ tumors with injectable lesions (Phase 1B, Arm 2, Cohort 3).

Related Conditions:
  • Anal Carcinoma
  • Cervical Carcinoma
  • Oropharyngeal Carcinoma
  • Penile Carcinoma
  • Vaginal Carcinoma
  • Vulvar Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: This is a Trial of MG1-E6E7 With Ad-E6E7 and Atezolizumab in Patients With HPV Associated Cancers
  • Official Title: Phase 1/1b, Multicenter, Open-label Trial of Oncolytic MG1 Virus (MG1-E6E7) With Adenovirus Vaccine (Ad-E6E7) Both Expressing Mutant Human Papilloma Virus (HPV) E6 and E7 and Atezolizumab in Pts With HPV Assoc. Cancers

Clinical Trial IDs

  • ORG STUDY ID: Ad-MG1-E6E7-002
  • NCT ID: NCT03618953

Conditions

  • HPV-Associated Cancers

Interventions

DrugSynonymsArms
Ad-E6E7Arm 1 (Intravenous dosing)
MG1-E6E7Arm 1 (Intravenous dosing)
AtezolizumabTecentriqArm 1 (Intravenous dosing)

Purpose

This is a Phase 1/1b open-label dose escalation trial of Ad/MG1-E6E7 and sequential treatment with atezolizumab in patients with HPV associated cancers. This study will consist of two arms. Both arms will dose escalate (MG1-E6E7) using a 3 + 3 design in Phase 1 to establish initial safety and the maximum tolerated dose (MTD) / maximum feasible dose (MFD). - Arm 1 - intravenous (IV) administration of MG1-E6E7 following intramuscular (IM) AD-E6E7 priming and subsequent treatment with IV atezolizumab. - Arm 2 - intratumoral (IT) and IV injection of MG1-E6E7 following (IM) Ad-E6E7 priming and subsequent treatment with IV atezolizumab. In the Phase 1b expansion for each arm, additional patients will be enrolled at the MTD as determined in Phase 1 in order to more thoroughly explore immune response, pharmacokinetics/dynamics, and safety for the patient populations with Cervical cancer, HPV positive (HPV+) Oropharyngeal cancer (Phase 1B, Arm 1, Cohorts A and B respectively) and HPV+ tumors with injectable lesions (Phase 1B, Arm 2, Cohort 3).

Trial Arms

NameTypeDescriptionInterventions
Arm 1 (Intravenous dosing)ExperimentalFixed dose of Ad-E6E7 administered IM on study Day 1. Followed by one of 3 dose levels (escalation) of MG1-E6E7 administered as 4 infusion (IV) doses over 2 weeks starting at study day 15. Fixed dose of atezolizumab administered IV every 3weeks starting at study day 43.
    Arm 2 (Intravenous and Intra-tumoral injection dosing)ExperimentalFixed dose of Ad-E6E7 administered IM on study Day 1. Followed by one of 2 dose levels (escalation) of MG1-E6E7 administered as 1 IV dose, starting at study day 15, followed by 2 intratumoral (IT) doses administered on study days 18 & 29. Fixed dose of atezolizumab administered IV every 3weeks starting at study day 43.

      Eligibility Criteria

              Key Inclusion Criteria:
      
                -  Histologically or cytologically confirmed recurrent or metastatic HPV associated tumor
                   (cervical, oropharyngeal, vulvar, vaginal, anal, or penile) with documented disease
                   progression.
      
                -  Arm 1, Phase 1 dose escalation: Cervical, HPV+ oropharyngeal, vulvar, vaginal, anal,
                   or penile
      
                -  Arm 1, Cohort A: Cervical cancer
      
                -  Arm 1, Cohort B: HPV+ Oropharyngeal cancer
      
                -  Arm 2 Phase 1 dose escalation and Cohort C: Cervical, oropharyngeal, vulvar, vaginal,
                   anal, or penile
      
                -  Failed, refused or intolerant to systemic therapy
      
                -  Measurable disease based on RECIST 1.1
      
                -  At least one tumor mass amenable to core needle biopsy
      
                -  Arm 2 only: At least one tumor judged as being safely injectable
      
                -  ECOG performance status 0 or 1
      
                -  Demonstrate adequate organ function
      
                -  Additional Inclusion criteria exist
      
              Key Exclusion Criteria:
      
                -  Prior systemic therapy within 4 weeks.
      
                -  Patients receiving prior XRT must have recovered from any acute toxicity.
      
                -  Currently receiving/received experimental therapy within 4 weeks.
      
                -  Prior treatment with any HPV vaccine therapy for cancer.
      
                -  Requires use of anti-platelet or anti-coagulant therapy that cannot be safely
                   suspended for per protocol biopsies or intra-tumoral injections.
      
                -  Known active CNS metastases and/or carcinomatous meningitis.
      
                -  Clinically significant tumor invasion/ rapidly accumulating ascites, pericardial or
                   pleural effusions.
      
                -  Active infection requiring systemic therapy.
      
                -  Active autoimmune disease that has required systemic therapy in the past 2 years.
      
                -  Conditions likely to have resulted in splenic dysfunction.
      
                -  Known HIV/AIDS, active HBV or HCV infection.
      
                -  Received prior treatment with vesicular stomatitis (VSV) viral vector.
      
                -  Received immunosuppressive medication within 4 weeks. (>10mg/day prednisone)
      
                -  ≥ Grade 2 dyspnea and/or require supplemental oxygen
      
                -  Known intolerance to anti-PD-1 or anti-PD-L1 antibody therapy
      
                -  Additional Exclusion criteria exist
      
              Exclusion Criteria Household Contacts:
      
                -  Patients with household contacts meeting any of the following criteria are ineligible
                   for study entry unless alternate living arrangements can be made, while under contact
                   precautions.
      
                -  Women who are pregnant or nursing an infant
      
                -  Children < 1 year old
      
                -  Individuals who are severely immunocompromised
      
                -  Contact precautions are from initial treatment with MG1-E6E7 to 7 days after the last
                   dose of MG1-E6E7
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Safety of Ad/MG1-E6E7 administration in HPV associated cancers
      Time Frame:8 months
      Safety Issue:
      Description:Safety will be determined by assessing the severity and frequency of treatment emergent Adverse Events and clinical laboratory toxicity using NCI CTCAE v 4.03.

      Secondary Outcome Measures

      Measure:Concentration of Ad/MG1-E6E7 in blood
      Time Frame:4 to 6 weeks after first treatment with Ad/MG1-E6E7
      Safety Issue:
      Description:Change over time in the number of MG1-E6E7 genomes (qPCR) and MG1-E6E7 infectious units (PFU) in blood
      Measure:Assess for the biodistribution and shedding of Ad/MG1-E6E7
      Time Frame:6 weeks after first treatment with Ad/MG1-E6E7
      Safety Issue:
      Description:Determine if there is any shedding of Ad/MG1-E6E7 into the environment by detecting the presence of viral plaque forming units (PFUs) in urine samples, cheek swabs, and rectal swabs after Ad/MG1-E6E7 treatment
      Measure:Measure the differences in pre- and post treatment levels of T cell subsets and T cell activation status
      Time Frame:Before and after each dose of Ad/MG1-E6E7 and then every 3 weeks until treatment discontinuation
      Safety Issue:
      Description:Analyze the change over time in the the frequencies, absolute numbers and subsets of T cells (including regulatory T cells)
      Measure:Anti-tumor activity
      Time Frame:Every 6 weeks for the first course of treatment and then every 9 weeks until date of documented progression by irRECIST, up to 2 years
      Safety Issue:
      Description:Evaluate tumor response by CT scan using RECIST v1.1 and irRECIST criteria in the overall patient population and the HPV16/18 positive patient population

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Turnstone Biologics, Inc.

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