Department of Neurosurgery, School of Medicine, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea.
Department of Medicine, Division of Hematology-Oncology, School of Medicine, Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea.
Cancer Med. 2023 Aug;12(15):15788-15796. doi: 10.1002/cam4.6213. Epub 2023 Aug 3.
We evaluated the therapeutic efficacy of GC1118, a novel anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification.
This study was a multicenter, open-label, single-arm phase II trial. Recurrent GBM patients with EGFR amplification were eligible: EGFR amplification was determined using fluorescence in situ hybridization analysis when a sample had both the EGFR/CEP7 ratio of ≥2 and a tight cluster EGFR signal in ≥10% of recorded cells. GC1118 was administered intravenously at a dose of 4 mg/kg once weekly. The primary endpoint was the 6-month progression-free survival rate (PFS6). Next-generation sequencing was performed to investigate the molecular biomarkers related to the response to GC1118.
Between April 2018 and December 2020, 21 patients were enrolled in the study and received GC1118 treatment. Eighteen patients were eligible for efficacy analysis. The PFS6 was 5.6% (95% confidence interval, 0.3%-25.8%, Wilson method). The median progression-free survival was 1.7 months (range: 28 days-7.2 months) and median overall survival was 5.7 months (range: 2-22.0 months). GC1118 was well tolerated except skin toxicities. Skin rash was the most frequent adverse event and four patients experienced Grade 3 skin-related toxicity. Genomic analysis revealed that the immune-related signatures were upregulated in patients with tumor regression.
This study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune-mediated antitumor efficacy of GC1118.
我们评估了新型抗表皮生长因子受体（EGFR）单克隆抗体 GC1118 在 EGFR 扩增的复发性胶质母细胞瘤（GBM）患者中的治疗效果。
这是一项多中心、开放标签、单臂 II 期试验。符合条件的复发性 GBM 患者 EGFR 扩增：使用荧光原位杂交分析确定 EGFR 扩增，当 EGFR/CEP7 比值≥2 且记录的细胞中≥10%的细胞存在紧密簇 EGFR 信号时。GC1118 以 4mg/kg 的剂量静脉注射，每周一次。主要终点是 6 个月无进展生存期（PFS6）。进行下一代测序以研究与 GC1118 反应相关的分子生物标志物。
2018 年 4 月至 2020 年 12 月，共有 21 名患者入组并接受 GC1118 治疗。18 名患者符合疗效分析标准。PFS6 为 5.6%（95%置信区间，0.3%-25.8%，Wilson 法）。中位无进展生存期为 1.7 个月（范围：28 天-7.2 个月），中位总生存期为 5.7 个月（范围：2-22.0 个月）。除皮肤毒性外，GC1118 耐受性良好。皮疹是最常见的不良事件，有 4 名患者发生 3 级皮肤相关毒性。基因组分析显示，在 GC1118 治疗后肿瘤消退的患者中，免疫相关特征上调。
本研究未达到主要终点（PFS6）；然而，我们发现 GC1118 治疗后肿瘤消退的患者中免疫特征显著上调，这表明 GC1118 具有潜在的免疫介导的抗肿瘤疗效。
