Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer
Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer
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DOI：
10.1038/s41417-021-00317-5
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发表时间：
2021-03-22
影响因子：
6.4
通讯作者：
Nemunaitis, John
中科院分区：
文献类型：
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作者：
Rocconi, Rodney P.;Stevens, Erin E.;Nemunaitis, John
VIGIL(R)是一种个性化疫苗，可增强肿瘤新抗原的表达。我们首次研究了Vigil联合阿替唑单抗治疗复发性卵巢癌(OC)的安全性和有效性。这是一项关于Vigil的随机第一阶段研究，Vigil是一种自体肿瘤组织转基因疫苗，编码GMCSF和bi-shRNA-Furin，从而增强免疫激活和控制转化生长因子β的表达。第一部分是Vigil(1×10e7细胞/毫升/21天)加阿替唑珠单抗(1200 mg/21天)的安全性评估。第二部分是两个周期的Vigil First(Vigil-first)或atezolizumab First(Atezo-first)的随机研究，然后联合使用这两种药物。该研究的主要终点是安全性的确定。24名患者参加了这项研究；3名患者进入第一部分，21名患者进入第二部分。第一部分的患者完成了没有剂量限制性毒性的联合治疗，证明扩展到第二部分是合理的。21名患者被随机(1：1)分成第二部分至Vigil-first(n=11)或Atezo-first(n=10)。Atezo-1与Vigil-1的3/4级治疗相关不良事件分别为17.2%和5.1%。中位总生存期(OS)未达到(NR)(Vigil-1)，而Atezo-1(Atezo-1)为10.8个月(风险比[HR]0.33)。BRCA(Wt)的探索性子集分析表明，OS受益有所改善[在Vigil-1与ATEZO-1相比，NR为5.2个月，HR为0.16，p 0.027]。Vigil-First与阿替唑单抗的联合治疗是安全的，并导致在BRCA(Wt)患者中进行支持性继续研究。
Vigil (R) is a personalized vaccine that enhances tumor neoantigen expression. We investigated for the first time safety and efficacy of Vigil in combination with atezolizumab in relapsed ovarian cancer (OC) patients. This is a randomized, Phase 1 study of Vigil, an autologous tumor tissue transfected vaccine encoding for GMCSF and bi-shRNA-furin thereby creating enhanced immune activation and TGF beta expression control. Part 1 is a safety assessment of Vigil (1 x 10e7 cells/mL/21 days) plus atezolizumab (1200 mg/21 days). Part 2 is a randomized study of Vigil first (Vigil-1st) or atezolizumab first (Atezo-1st) for two cycles followed by the combination of both agents. The primary endpoint of the study was the determination of safety. Twenty-four patients were enrolled in the study; three patients to Part 1 and 21 to Part 2. Patients in Part 1 completed combination therapy without dose-limiting toxicity justifying expansion to Part 2. Twenty-one patients were randomized (1:1) to Part 2 to Vigil-1st (n = 11) or Atezo-1st (n = 10). Grade 3/4 treatment-related adverse events of Atezo-1st vs. Vigil-1st were 17.2% vs. 5.1%. Median overall survival (OS) was not reached (NR) (Vigil-1st) vs. 10.8 months (Atezo-1st) (hazard ratio [HR] 0.33). The exploratory subset analysis of BRCA(wt) suggested improved OS benefit [NR in Vigil-1st vs. 5.2 months in Atezo-1st, HR 0.16, p 0.027]. The Vigil-1st combination therapy with atezolizumab was safe and results in support continued investigation in BRCA(wt) patients.