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

Turnstone Biologics

Status and phase: Terminated; Phase 1

Conditions: HPV-Associated Cancers

Treatments: Biological: Ad-E6E7; Biological: Atezolizumab; Biological: MG1-E6E7

Study type: Interventional

Funder types: Industry

Identifiers

NCT03618953

Ad-MG1-E6E7-002

Details and patient eligibility

About

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).

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

Arm 1 (Intravenous dosing)

Experimental group

Description:

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.

Treatment:

Biological: MG1-E6E7

Biological: Atezolizumab

Biological: Ad-E6E7

Arm 2 (Intravenous and Intra-tumoral injection dosing)

Experimental group

Description:

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.

Treatment:

Biological: MG1-E6E7

Biological: Atezolizumab

Biological: Ad-E6E7