STING Agonist and Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy in Combination With Checkpoint Inhibition for Patients With Metastatic Kidney Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- To evaluate the PFS rate associated with the therapeutic intervention. PFS is defined as the duration of time from initiation of PULSAR/IMSA101 to disease progression as defined by RECIST1.1 or death.
研究概览
简要总结
To evaluate the impact of combining innate immune system activation (with IMSA101) with antigen release (through SAbR/PULSAR) on limited progressing lesions during ongoing adaptive immune system activation (with maintenance Nivo).
详细描述
The study expects to accrue the 15 patients over a 3-4 year period.
Patients with oligoprogressive disease (≤5 lesions) after treatment with Anti-PD1 / Anti-CTLA-4 will continue Anti-PD1 (nivolumab). All patients will have a mandatory PD-L1 PET (Pre-treatment and Week 12). All patients will undergo baseline biopsy (just before the administration of IMSA101 of the same lesion to be injected). SAbR will be delivered in 3 fractions at 12 Gy every 4 weeks (PULSAR regimen) to all progressing lesions. One lesion will also receive 3 intratumoral injections of IMSA101 (C1D1, C1D8, C1D15, C2D1, C3D1) immediately after radiation either on the same day or within 72 hours after the PULSE.
Selected Phase 2 dosing of IMSA101 (1200mcg) will be utilized.
At disease progression, patients have the option to undergo additional imaging and tissue/blood collections.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients must have metastatic ccRCC.
- •Patients must have oligoprogression defined as progression in ≤5 lesions.
- •All oligoprogression lesions must be suitable for radiation.
- •Patients must have at least one site of disease that can be safely injected with IMSA
- •Karnofsky Performance Status (KPS) of at least 50%.
- •Age ≥ 18 years.
- •Patients must have adequate organ and marrow function within 14 days prior to study entry.
- •All IMDC risk categories are allowed.
排除标准
- •Patients with progressive ultracentral/central chest lesions will be excluded
研究组 & 干预措施
SAbR with Intratumoral STING agonist IMSA101 and IO with Anti-PD1
Only one arm will be maintained in this phase II study with all patients undergoing the following treatment:
SOC treatment: Nivolumab 480 mg monthly PULSAR: 36 Gy in 3 fractions, Q4weeks IMSA101: three intra-tumoral injections of one of the progressive lesions at 1200 mcg (C1D1, C2D1, C3D1)
干预措施: IMSA101 (Drug)
结局指标
主要结局
To evaluate the PFS rate associated with the therapeutic intervention. PFS is defined as the duration of time from initiation of PULSAR/IMSA101 to disease progression as defined by RECIST1.1 or death.
时间窗: Time from initiation of PULSAR/IMSA101 until death from any cause. Follow-up visits to be done every 12 weeks (+/- 1 week) for study duration until patient has progressed. Afterward, subjects to be contacted every 6 months for survival data up to 5 years
Exact binomial test will be used to test if the lower limit of the 95% confidence interval of the probability of postponing systemic therapy \>9 months will be greater than 30%.
次要结局
未报告次要终点
研究者
Raquibul Hannan
MD
University of Texas Southwestern Medical Center