Department of Neurological Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
Imvax, Inc., Philadelphia, Pennsylvania.
Clin Cancer Res. 2021 Apr 1;27(7):1912-1922. doi: 10.1158/1078-0432.CCR-20-3805. Epub 2021 Jan 26.
Despite standard of care (SOC) established by Stupp, glioblastoma remains a uniformly poor prognosis. We evaluated IGV-001, which combines autologous glioblastoma tumor cells and an antisense oligonucleotide against IGF type 1 receptor (IMV-001), in newly diagnosed glioblastoma.
This open-label protocol was approved by the Institutional Review Board at Thomas Jefferson University. Tumor cells collected during resection were treated with IMV-001, encapsulated in biodiffusion chambers with additional IMV-001, irradiated, then implanted in abdominal acceptor sites. Patients were randomized to four exposure levels, and SOC was initiated 4-6 weeks later. On the basis of clinical improvements, randomization was halted after patient 23, and subsequent patients received only the highest exposure. Safety and tumor progression were primary and secondary objectives, respectively. Time-to-event outcomes were compared with the SOC arms of published studies.
Thirty-three patients were enrolled, and median follow-up was 3.1 years. Six patients had adverse events (grade ≤3) possibly related to IGV-001. Median progression-free survival (PFS) was 9.8 months in the intent-to-treat population (vs. SOC, 6.5 months; = 0.0003). In IGV-001-treated patients who met Stupp-eligible criteria, PFS was 11.6 months overall ( = 22; = 0.001) and 17.1 months at the highest exposure ( = 10; = 0.0025). The greatest overall survival was observed in Stupp-eligible patients receiving the highest exposure (median, 38.2 months; = 0.044). Stupp-eligible patients with methylated O-methylguanine-DNA methyltransferase promoter ( = 10) demonstrated median PFS of 38.4 months ( = 0.0008). Evidence of immune activation was noted.
IGV-001 was well tolerated, PFS compared favorably with SOC, and evidence suggested an immune-mediated mechanism (ClinicalTrials.gov: NCT02507583).
尽管 Stupp 确立了标准治疗（SOC），但胶质母细胞瘤的预后仍然很差。我们评估了 IGV-001，它将自体胶质母细胞瘤肿瘤细胞与针对 IGF 型 1 受体的反义寡核苷酸（IMV-001）结合使用，用于新诊断的胶质母细胞瘤。
该开放性研究方案获得了托马斯·杰斐逊大学机构审查委员会的批准。在切除过程中收集的肿瘤细胞用 IMV-001 处理，然后将其封装在生物扩散室中，并添加额外的 IMV-001、照射，然后植入腹部接受部位。患者随机分为四个暴露水平，SOC 在 4-6 周后开始。根据临床改善，在第 23 位患者后停止随机分组，随后的患者仅接受最高暴露。安全性和肿瘤进展分别是主要和次要目标。时间事件结果与已发表研究的 SOC 臂进行了比较。
共纳入 33 例患者，中位随访时间为 3.1 年。6 例患者出现可能与 IGV-001 相关的不良事件（≤3 级）。意向治疗人群的中位无进展生存期（PFS）为 9.8 个月（SOC 为 6.5 个月；P=0.0003）。在符合 Stupp 标准的 IGV-001 治疗患者中，总体 PFS 为 11.6 个月（P=22；P=0.001），最高暴露组为 17.1 个月（P=10；P=0.0025）。在接受最高暴露的符合 Stupp 标准的患者中观察到最大的总生存（中位 38.2 个月；P=0.044）。甲基化 O-甲基鸟嘌呤-DNA 甲基转移酶启动子的符合 Stupp 标准的患者（P=10）中位 PFS 为 38.4 个月（P=0.0008）。观察到免疫激活的证据。
IGV-001 耐受性良好，PFS 优于 SOC，并有证据表明存在免疫介导的机制（ClinicalTrials.gov：NCT02507583）。
