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

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

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).

Study Overview

• Status: Terminated
• Conditions: HPV-Associated Cancers
• Intervention / Treatment: Biological: Ad-E6E7; Biological: MG1-E6E7; Biological: Atezolizumab

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M5G 1X6
      • Princess Margaret Hospital
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Toledo, Ohio, United States, 43614
      • University of Toledo-The Eleanor N. Dana Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas-MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: Tecentriq

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Ad/MG1-E6E7 administration in HPV associated cancers	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.	8 months
Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-E6E7 in HPV associated cancers	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	4 to 6 weeks after first treatment with Ad/MG1-E6E7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Ad/MG1-E6E7 in blood	Change over time in the number of MG1-E6E7 genomes (qPCR) and MG1-E6E7 infectious units (PFU) in blood	4 to 6 weeks after first treatment with Ad/MG1-E6E7
Assess for the biodistribution and shedding of 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	6 weeks after first treatment with Ad/MG1-E6E7
Measure the differences in pre- and post treatment levels of T cell subsets and T cell activation status	Analyze the change over time in the the frequencies, absolute numbers and subsets of T cells (including regulatory T cells)	Before and after each dose of Ad/MG1-E6E7 and then every 3 weeks until treatment discontinuation
Anti-tumor activity	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	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

Collaborators and Investigators

• Sponsor: Turnstone Biologics, Corp.

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2018
• Primary Completion (Actual): March 5, 2021
• Study Completion (Actual): March 5, 2021

Study Registration Dates

• First Submitted: June 22, 2018
• First Submitted That Met QC Criteria: August 1, 2018
• First Posted (Actual): August 7, 2018

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Atezolizumab
• Other Study ID Numbers: Ad-MG1-E6E7-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No