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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 15
- 主要终点
- Safety of Ad/MG1-E6E7 administration in HPV associated cancers
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Safety of Ad/MG1-E6E7 administration in HPV associated cancers
时间窗: 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
时间窗: 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
次要结局
- 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)
- 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)
- Assess for the biodistribution and shedding of Ad/MG1-E6E7(6 weeks after first treatment with Ad/MG1-E6E7)
- Concentration of Ad/MG1-E6E7 in blood(4 to 6 weeks after first treatment with Ad/MG1-E6E7)