this is a trial of mg1-e6e7 with ad-e6e7 and atezolizumab in patients with hpv associated cancers

Conditions: HPV-Associated Cancers

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