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

NCT03618953 | Terminated Phase 1 FDA Drug

• 1 other identifier: Ad-MG1-E6E7-002
• Study Type: interventional
• Target: 8
• Locations: 2 countries
• Sites: 8

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Concentration of Ad/MG1-E6E7 in blood

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

• Assess for the biodistribution and shedding of Ad/MG1-E6E7

  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

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

• Anti-tumor activity

  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

Study Arms (2)

Arm 1 (Intravenous dosing)

EXPERIMENTAL

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; Biological: MG1-E6E7; Biological: Atezolizumab

Arm 2 (Intravenous and Intra-tumoral injection dosing)

EXPERIMENTAL

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; Biological: MG1-E6E7; Biological: Atezolizumab

Interventions

Ad-E6E7 BIOLOGICAL

Adenovirus vaccine expressing mutant HPV E6 and E7

Arm 1 (Intravenous dosing); Arm 2 (Intravenous and Intra-tumoral injection dosing)

MG1-E6E7 BIOLOGICAL

MG1 Maraba oncolytic virus expressing mutant HPV E6 and E7

Arm 1 (Intravenous dosing); Arm 2 (Intravenous and Intra-tumoral injection dosing)

Atezolizumab BIOLOGICAL

monoclonal antibody; checkpoint inhibitor

Also known as: Tecentriq

Arm 1 (Intravenous dosing); Arm 2 (Intravenous and Intra-tumoral injection dosing)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Turnstone Biologics, Corp.: lead

Study Sites (8)

University of Miami

Miami, Florida, 33136, United States

Location

Billings Clinic

Billings, Montana, 59101, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Toledo-The Eleanor N. Dana Cancer Center

Toledo, Ohio, 43614, United States

Location

University of Texas-MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 1X6, Canada

Location

MeSH Terms

Interventions

atezolizumab

Study Officials

• Steve Bernstein, MD

  Turnstone Biologics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: August 7, 2018
• Study Start: June 21, 2018
• Primary Completion: March 5, 2021
• Study Completion: March 5, 2021
• Last Updated: April 14, 2023

Record last verified: 2023-04

Locations

US (5); CA (3)