HPV-Associated Cancers
Conditions
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).
Interventions
BIOLOGICALAd-E6E7
Adenovirus vaccine expressing mutant HPV E6 and E7
BIOLOGICALMG1-E6E7
MG1 Maraba oncolytic virus expressing mutant HPV E6 and E7
BIOLOGICALAtezolizumab
monoclonal antibody; checkpoint inhibitor
Sponsors
Turnstone Biologics, Corp.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
Countries
Canada, United States
Outcome results
None listed