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

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ClinicalTrials.gov Identifier: NCT03618953
Recruitment Status : Recruiting
First Posted : August 7, 2018
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Turnstone Biologics, Inc.

Brief Summary:

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).


Condition or disease Intervention/treatment Phase
HPV-Associated Cancers Biological: Ad-E6E7 Biological: MG1-E6E7 Biological: Atezolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 21, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1 (Intravenous dosing)

Fixed 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.

Biological: Ad-E6E7
Adenovirus vaccine expressing mutant HPV E6 and E7

Biological: MG1-E6E7
MG1 Maraba oncolytic virus expressing mutant HPV E6 and E7

Biological: Atezolizumab
monoclonal antibody; checkpoint inhibitor
Other Name: Tecentriq

Experimental: Arm 2 (Intravenous and Intra-tumoral injection dosing)

Fixed 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.

Biological: Ad-E6E7
Adenovirus vaccine expressing mutant HPV E6 and E7

Biological: MG1-E6E7
MG1 Maraba oncolytic virus expressing mutant HPV E6 and E7

Biological: Atezolizumab
monoclonal antibody; checkpoint inhibitor
Other Name: Tecentriq




Primary Outcome Measures :
  1. Safety of Ad/MG1-E6E7 administration in HPV associated cancers [ Time Frame: 8 months ]
    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.

  2. Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-E6E7 in HPV associated cancers [ Time Frame: 4 to 6 weeks after first treatment with Ad/MG1-E6E7 ]
    MTD/MFD of Ad/MG1-E6E7 administered by IV infusion alone and IV infusion followed by direct injection of tumor (IT injection) in HPV associated cancers


Secondary Outcome Measures :
  1. Concentration of Ad/MG1-E6E7 in blood [ Time Frame: 4 to 6 weeks after first treatment with Ad/MG1-E6E7 ]
    Change over time in the number of MG1-E6E7 genomes (qPCR) and MG1-E6E7 infectious units (PFU) in blood

  2. Assess for the biodistribution and shedding of Ad/MG1-E6E7 [ Time Frame: 6 weeks after first treatment with Ad/MG1-E6E7 ]
    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

  3. 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 ]
    Analyze the change over time in the the frequencies, absolute numbers and subsets of T cells (including regulatory T cells)

  4. 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 ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT03618953


Contacts
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Contact: Tara Hollister - Clinical Trial Assistant 613-983-8272 tara.hollister@turnstonebio.com
Contact: Huguette Graham - Documentation Specialist 613-421-8930 ext 229 huguette.graham@turnstonebio.com

Locations
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United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact       clinicalops@turnstonebio.com   
United States, Montana
Billings Clinic Recruiting
Billings, Montana, United States, 59101
Contact: Kelsey Skogen    406-435-7443      
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Ryan Gardner    646-888-5097    gardner1@mskcc.org   
Principal Investigator: Dmitriy Zamarin, MD         
United States, Ohio
University of Toledo-The Eleanor N. Dana Cancer Center Recruiting
Toledo, Ohio, United States, 43614
Contact: Stephanie Smiddy    419-383-6962    Stephanie.smiddy@utoledo.edu   
Contact: Jill Sholl    419 383-4553    Jill.sholl@utoledo.edu   
Principal Investigator: John Nemunaitis, MD         
United States, Texas
University of Texas-MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Jisha Mathews    713-745-9919    jmathews2@mdanderson.org   
Principal Investigator: Bonnie Glisson, MD         
Canada, Ontario
Juravinski Cancer Centre Not yet recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Yvonne Kinrade    905-387-9711 ext 64402    ykinrade@HHSC.ca   
Principal Investigator: Sebastien Hotte, MD         
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Derek Jonker    613-737-7700    djonker@toh.ca   
Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 1X6
Contact: Chantale Blattler    416-946-4501 ext 3692    chantale.blattler@uhn.ca   
Principal Investigator: Amit Oza, MD         
Sponsors and Collaborators
Turnstone Biologics, Inc.
Investigators
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Study Director: Steve Bernstein, MD Turnstone Biologics

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Responsible Party: Turnstone Biologics, Inc.
ClinicalTrials.gov Identifier: NCT03618953     History of Changes
Other Study ID Numbers: Ad-MG1-E6E7-002
First Posted: August 7, 2018    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs