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

HPV-Associated Cancers Clinical Trial

— Kingfisher  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03618953
• Other study ID #: Ad-MG1-E6E7-002
• Status: Terminated
• Phase: Phase 1
• Start date: June 21, 2018
• Est. completion date: March 5, 2021

Study information

• Verified date: April 2023
• Source: Turnstone Biologics, Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: March 5, 2021
• Est. primary completion date: March 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HPV-Associated Cancers

Intervention

Biological:
• Ad-E6E7
Adenovirus vaccine expressing mutant HPV E6 and E7
• MG1-E6E7
MG1 Maraba oncolytic virus expressing mutant HPV E6 and E7
• Atezolizumab
monoclonal antibody; checkpoint inhibitor

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Billings Clinic	Billings	Montana
United States	University of Texas-MD Anderson Cancer Center	Houston	Texas
United States	University of Miami	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Toledo-The Eleanor N. Dana Cancer Center	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Turnstone Biologics, Corp.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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	4 to 6 weeks after first treatment with Ad/MG1-E6E7
Secondary	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	6 weeks after first treatment with Ad/MG1-E6E7
Secondary	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)	Before and after each dose of Ad/MG1-E6E7 and then every 3 weeks until treatment discontinuation
Secondary	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	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