A Phase 1/1b Study of VET3-TGI Administered Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 7
- 主要终点
- Incidence of dose limiting toxicities reported with VET3-TGI alone or in combination with pembrolizumab
研究概览
简要总结
VET3-TGI is an oncolytic immunotherapy designed to treat advanced cancers. VET3-TGI has not been given to human patients yet, and the current study is designed to find a safe and effective dose of VET3-TGI when administered by direct injection into tumor(s) (called an intratumoral injection) or when given intravenously (into the vein) both alone and in combination with pembrolizumab in patients with solid tumors (STEALTH-001).
详细描述
VET3-TGI was changed in a laboratory to infect and kill cancer cells, leaving healthy cells alone. This is a Phase 1 dose escalation (and expansion) study with VET3-TGI administered by direct injection into tumor(s) or by intravenous infusion. The dose escalation has 4 groups: the first group (Group A) will determine the highest tolerated dose of VET3-TGI when injected into tumor(s); the second group (Group C) will determine the highest tolerated dose of VET3-TGI when infused into the vein. The third and fourth groups (Group B and D) will combine VET3-TGI with pembrolizumab. These groups will begin at the highest tolerated dose determined in Group B and Group D, respectively.
Once the highest tolerated dose is found for each of these groups, that dose may be expanded to up to 15 additional patients to better examine the efficacy of VET3-TGI.
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
- •Have pathologically confirmed, advanced, unresectable, or metastatic solid tumors. Preferred indications include, but are not limited to, breast carcinoma, bladder carcinoma, cervical squamous carcinoma, colorectal carcinoma, esophageal carcinoma, head and neck squamous carcinoma, renal cell carcinoma, ovarian carcinoma, sarcoma, thymoma, and uterine carcinoma.
- •Failed, intolerant to, or refused potentially curative treatment options, including but not limited to, standard of care molecularly targeted agents, immunotherapy (e.g., anti -pembrolizumab/PDL1 antibodies), and chemotherapy
- •Measurable disease as per RECIST 1.1 criteria
- •At least one tumor amenable to safe ITu injections and/or biopsies
- •ECOG performance status 0 or 1
- •Demonstrate adequate organ function
- •Must be willing to comply with all protocol procedures and adhere to post-treatment care instructions
- •Additional Inclusion criteria exist
排除标准
- •Prior systemic therapy washout (dependent upon the therapy)
- •Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies or intra-tumoral injections.
- •CNS metastases and/or carcinomatous meningitis that have not been completely resected or completely irradiated.
- •Prior history of myocarditis
- •Known HIV/AIDS, active HBV or HCV infection.
- •Receiving high dose immunosuppressive medication or has a significant immunodeficiency (e.g. transplant recipient, etc).
- •Additional Exclusion criteria exist
研究组 & 干预措施
Group A: VET3-TGI alone intratumoral
Dose escalation of VET3-TGI alone administered by direct injection into tumor(s) x 4. Booster injections of VET3-TGI are permitted for up to 2 years.
干预措施: VET3-TGI (Drug)
Group B: VET3-TGI intratumoral in combination with pembrolizumab
VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group A. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.
干预措施: VET3-TGI (Drug)
Group B: VET3-TGI intratumoral in combination with pembrolizumab
VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group A. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.
干预措施: Pembrolizumab (Drug)
Group C: VET3-TGI alone intravenous
Dose escalation of VET3-TGI alone administered by IV infusion x 6. Booster infusions of VET3-TGI are permitted for up to 2 years.
干预措施: VET3-TGI (Drug)
Group D: VET3-TGI intravenous in combination with pembrolizumab
VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group C. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.
干预措施: VET3-TGI (Drug)
Group D: VET3-TGI intravenous in combination with pembrolizumab
VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group C. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities reported with VET3-TGI alone or in combination with pembrolizumab
时间窗: 4 weeks
Number of dose limiting toxicities, as defined in the protocol, by dose group
Incidence of adverse events with VET3-TGI alone or in combination with pembrolizumab
时间窗: 108 months
Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0
Determine the recommended Phase 2 dose
时间窗: 4 weeks
he highest dose of VET3-TGI in each group that can be administered where fewer than 2 patients have a dose-limiting safety event alone or when combined with pembrolizumab as assessed by NCI CTCAE v.5.0 during the Phase 1 dose escalation
次要结局
- Efficacy assessment: Duration of response (DOR)(108 months)
- Efficacy assessment: Time to tumor progression (TTP)(108 months)
- Efficacy assessment: disease control rate (DCR)(108 months)
- Overall survival(108 months)
- Efficacy assessment: Progression free survival (PFS)(108 months)
- Immune changes in tissue and blood(6 weeks)
- VET3-TGI delivery and replication kinetics(6 weeks)
- Efficacy assessment: overall response rate (ORR)(108 months)