This is a Trial of MG1-E6E7 With Ad-E6E7 and Atezolizumab in Patients With HPV Associated Cancers
- Conditions
- HPV-Associated Cancers
- Interventions
- Biological: Ad-E6E7Biological: MG1-E6E7Biological: Atezolizumab
- Registration Number
- NCT03618953
- Lead Sponsor
- Turnstone Biologics, Corp.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 8
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 (Intravenous and Intra-tumoral injection dosing) Atezolizumab 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. Arm 2 (Intravenous and Intra-tumoral injection dosing) MG1-E6E7 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. Arm 1 (Intravenous dosing) Atezolizumab 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. Arm 2 (Intravenous and Intra-tumoral injection dosing) Ad-E6E7 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. Arm 1 (Intravenous dosing) Ad-E6E7 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. Arm 1 (Intravenous dosing) MG1-E6E7 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.
- Primary Outcome Measures
Name Time Method Safety of Ad/MG1-E6E7 administration in HPV associated cancers 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.
Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-E6E7 in HPV associated cancers 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
Name Time Method 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 Analyze the change over time in the the frequencies, absolute numbers and subsets of T cells (including regulatory T cells)
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 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
Assess for the biodistribution and shedding of Ad/MG1-E6E7 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
Concentration of Ad/MG1-E6E7 in blood 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
Trial Locations
- Locations (8)
Billings Clinic
🇺🇸Billings, Montana, United States
University of Texas-MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Toledo-The Eleanor N. Dana Cancer Center
🇺🇸Toledo, Ohio, United States
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Ottawa Hospital Research Institute
🇨🇦Ottawa, Ontario, Canada
University of Miami
🇺🇸Miami, Florida, United States