AzTrials
AzTrials

HPV-Associated CancersPhase 1KingfisherNCT03618953

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

A Phase 1 study testing Ad-E6E7, MG1-E6E7 and Atezolizumab in people with HPV-Associated Cancers, run by Turnstone Biologics, Corp. at 8 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HPV-Associated Cancers
What is being tested?
Ad-E6E7, MG1-E6E7 and Atezolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
8 sitesin 2 countries
Study dates
21 Jun 2018to 5 Mar 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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.
Show all 21Show fewer
  • 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
  • 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

Trial locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

United States5 sites

  • Billings Clinic

    Billings, Montana, 59101

  • University of Texas-MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Miami

    Miami, Florida, 33136

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Toledo-The Eleanor N. Dana Cancer Center

    Toledo, Ohio, 43614

Other trials in United States

Canada3 sites

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 5C2

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 1X6

Other trials in Canada

About this study

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

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).

Being tested
Ad-E6E7, MG1-E6E7, Atezolizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ad-E6E7Biological

    Adenovirus vaccine expressing mutant HPV E6 and E7

  • MG1-E6E7Biological

    MG1 Maraba oncolytic virus expressing mutant HPV E6 and E7

  • AtezolizumabBiological

    Also called Tecentriq

    monoclonal antibody; checkpoint inhibitor

Study groups in NCT03618953
Study groupRoleWhat they receive
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.
Receives: Biological: Ad-E6E7; Biological: MG1-E6E7; Biological: Atezolizumab
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.
Receives: Biological: Ad-E6E7; Biological: MG1-E6E7; Biological: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 8 months

  2. 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

    Measured: 4 to 6 weeks after first treatment with Ad/MG1-E6E7

Secondary outcomes (4)

  1. 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

    Measured: 4 to 6 weeks after first treatment with Ad/MG1-E6E7

  2. 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

    Measured: 6 weeks after first treatment with Ad/MG1-E6E7

  3. 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)

    Measured: Before and after each dose of Ad/MG1-E6E7 and then every 3 weeks until treatment discontinuation

  4. 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

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2018
  2. Study start21 Jun 2018
  3. Primary completion5 Mar 2021
  4. Study completion5 Mar 2021

Why it stopped: Virus potency titer of drug product as determined by an improved potency assay was lower than originally determined by the assay described in the IND.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03618953
Sponsor's protocol ID
Ad-MG1-E6E7-002
Acronym
Kingfisher
Status last verified
Apr 2023
First submitted
22 Jun 2018
Last updated
14 Apr 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ad-E6E7, MG1-E6E7 and Atezolizumab in people with HPV-Associated Cancers, run by Turnstone Biologics, Corp. at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Virus potency titer of drug product as determined by an improved potency assay was lower than originally determined by the assay described in the IND.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of Ad/MG1-E6E7 administration in HPV associated cancers (time frame: 8 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03618953.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in