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

NCT ID: NCT03618953

Last Updated: 2023-04-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-21
• Study Completion Date: 2021-03-05

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).

Conditions

HPV-Associated Cancers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ad-E6E7

Intervention Type: BIOLOGICAL

Adenovirus vaccine expressing mutant HPV E6 and E7

MG1-E6E7

Intervention Type: BIOLOGICAL

MG1 Maraba oncolytic virus expressing mutant HPV E6 and E7

Atezolizumab

Intervention Type: BIOLOGICAL

monoclonal antibody; checkpoint inhibitor

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.

Group Type: EXPERIMENTAL

Ad-E6E7

Intervention Type: BIOLOGICAL

Adenovirus vaccine expressing mutant HPV E6 and E7

MG1-E6E7

Intervention Type: BIOLOGICAL

MG1 Maraba oncolytic virus expressing mutant HPV E6 and E7

Atezolizumab

Intervention Type: BIOLOGICAL

monoclonal antibody; checkpoint inhibitor

Interventions

Ad-E6E7

Adenovirus vaccine expressing mutant HPV E6 and E7

Intervention Type: BIOLOGICAL

MG1-E6E7

MG1 Maraba oncolytic virus expressing mutant HPV E6 and E7

Intervention Type: BIOLOGICAL

Atezolizumab

monoclonal antibody; checkpoint inhibitor

Intervention Type: BIOLOGICAL

Other Intervention Names

Tecentriq

Eligibility Criteria

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

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Turnstone Biologics, Corp.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steve Bernstein, MD

Role: STUDY_DIRECTOR

Turnstone Biologics

Locations

University of Miami

Miami, Florida, United States

Billings Clinic

Billings, Montana, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Toledo-The Eleanor N. Dana Cancer Center

Toledo, Ohio, United States

University of Texas-MD Anderson Cancer Center

Houston, Texas, United States

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

Ad-MG1-E6E7-002

Identifier Type: -

Identifier Source: org_study_id