Clinical trial NCT03618953: This is a Trial of MG1-E6E7 With Ad-E6E7 and Atezolizumab in Patients With HPV Associated Cancers
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: HPV-Associated Cancers
Lead sponsor: Turnstone Biologics, Corp.
Sponsor class: INDUSTRY
First posted: 2018-08-07
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Safety of Ad/MG1-E6E7 administration in HPV associated cancers
timeFrame: 8 months
measure: Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-E6E7 in HPV associated cancers
timeFrame: 4 to 6 weeks after first treatment with Ad/MG1-E6E7
Secondary outcomes:
measure: Concentration of Ad/MG1-E6E7 in blood
timeFrame: 4 to 6 weeks after first treatment with Ad/MG1-E6E7
measure: Assess for the biodistribution and shedding of Ad/MG1-E6E7
timeFrame: 6 weeks after first treatment with Ad/MG1-E6E7
measure: Measure the differences in pre- and post treatment levels of T cell subsets and T cell activation status
timeFrame: Before and after each dose of Ad/MG1-E6E7 and then every 3 weeks until treatment discontinuation
measure: Anti-tumor activity
timeFrame: 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
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Toledo
country: United States
facility: University of Toledo-The Eleanor N. Dana Cancer Center
state: Ohio
city: Houston
country: United States
facility: University of Texas-MD Anderson Cancer Center
state: Texas
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Turnstone Biologics
name: Steve Bernstein, MD
role: STUDY_DIRECTOR
References: