A Phase 1/2, First-in-Human Study of VNX-202 Gene Therapy in Patients With HER2-Positive Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 27
- 试验地点
- 12
- 主要终点
- Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)
研究概览
简要总结
This is a Phase 1/2, first-in-human, open-label, dose-escalating and expansion trial designed to assess the safety and efficacy of VNX-202 in patients with HER2 positive cancers.
详细描述
VNX-202 is an investigational adeno-associated virus (AAV) gene therapy developed to express a secreted anti-HER2/anti-CD3 scFv diabody (termed GP202). GP202 binds to human epidermal growth factor receptor 2 (HER2) on the surface of cancer cells and to cluster of differentiation (CD)3 on the surface of T cells, inducing the T cells to kill the HER2-positive cancer cells.
Following a single intravenous (IV) infusion, the vector induces the liver to continuously secrete GP202 into the bloodstream, resulting in long-term, consistent serum levels of GP202. Compared with conventionally delivered protein therapies, this gene therapy approach obviates the requirement for episodic dosing and avoids a possible reduction or loss of efficacy associated with trough levels of the protein between treatment cycles.
In this 2-part study, dose-finding data from Part 1 of the study (n=~12 patients) will be used determine the dose for Part 2 in patients. Part 1 is a dose-finding PK study in adults ≥18 years old with previously treated metastatic HER2 solid tumors designed to determine the minimal dose that achieves target PK serum levels of GP202 at steady state (8-week timepoint) without dose-limited toxicities, defined as the recommended Part 2 dose (RP2D). Participants must have histologically or cytologically confirmed HER2 positive solid tumor cancers that has progressed during or following previous anti-cancer treatment. Part 2 (n=~15) will be opened following data safety monitoring board review of Part 1 data and is designed to determine the safety and pharmacokinetics (PK) of VNX-202 at the RP2D in a broader array of subjects. Part 2 will comprise of participants with early stage HER2-positive tumors who are at risk of disease relapse and/or metastasis despite having received prior systemic and/or local treatment. Each cohort will comprise ≥5 participants (Cohort A: breast cancer; Cohort B: gastric cancer; Cohort C: all otherHER2-positive tumor types). Patients will be followed for safety and efficacy up to 5 years post VNX-202 dosing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Age: ≥18 years of age
- •Histologically or cytologically confirmed diagnosis of HER-2 positive solid tumor as defined in the protocol
- •Part 1: presence of advanced or metastatic disease that has progressed during or following previous treatment
- •Part 2: Early stage HER-2 positive cancers with high risk for relapse following completion of SOC or after neoadjuvant systemic treatment
- •AAV specified capsid total antibody ≤1:400
- •ECOG performance status of 0 or 1
- •Life expectancy ≥3 months
- •Protocol-specified ranges for renal, liver, cardiac and pulmonary function
- •Protocol-specified ranges for hematology parameters
排除标准
- •Hepatoxicity (AST or ALT > 2x upper limit of normal)
- •Known active CNS or leptomeningeal disease
- •History of thrombotic microangiopathy or cardiomyopathy, or evidence of sensory neuropathy
- •Pregnant or nursing (lactating) women
- •History of other malignancy within 5 years prior to screening as defined in protocol
- •History of hypersensitivity to corticosteroids or history of corticosteroid-related toxicity Concurrent anti-cancer treatment in another investigational trial
研究组 & 干预措施
Group 1/Group 2/Group 3/Group 4
干预措施: Dose Level 2, VNX-202 (Genetic)
Group 1/Group 2/Group 3/Group 4
干预措施: Dose Level 1, VNX-202 (Genetic)
Group 1/Group 2/Group 3/Group 4
干预措施: Dose Level 4, VNX-202 (Genetic)
Group 1/Group 2/Group 3/Group 4
干预措施: Dose Level 3, VNX-202 (Genetic)
结局指标
主要结局
Treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)
时间窗: Change from Baseline to Year 5 post dosing
次要结局
- Change from baseline in ctDNA(Change from baseline to year 5 post dosing)
- Change from baseline in progression free survival(Change from baseline to year 5 post dosing)
- Change from baseline in overall survival(Change from baseline to year 5 post dosing)
- Change from baseline in T cell subsets and clonality(Change from baseline to year 5 post dosing)