A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma
A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma
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DOI：
10.3390/cancers12082270
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发表时间：
2020-08-01
期刊：
影响因子：
5.2
通讯作者：
Patel, Sapna
中科院分区：
文献类型：
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作者：
Hasanov, Merve;Rioth, Matthew J.;Patel, Sapna
Glembatumumab vedotin（CDX-011，GV）是一种针对糖蛋白NMB的全人源免疫球蛋白G2单克隆抗体，通过肽接头与一甲基澳瑞他汀E（MMAE）偶联，后者是一种强效细胞毒性微管抑制剂。这项II期研究评价了转移性葡萄膜黑色素瘤患者GV、糖蛋白NMB（GPNMB）表达和生存率的总体缓解率和安全性。既往未接受过化疗的符合条件的转移性葡萄膜黑色素瘤患者接受GV 1.9 mg/kg，每3周一次。主要终点为客观缓解率（ORR）。次要终点包括GPNMB表达、无进展生存期（PFS）、总生存期（OS）和毒性分析。对于具有可用肿瘤组织的患者，通过免疫组织化学在治疗前和治疗后评估GPNMB表达。在接受治疗的35例患者中，2例患者确认部分缓解（PR; 6%），18例患者的最佳客观缓解为疾病稳定（SD; 51%）。38%的患者病情稳定>100天。2例或2例以上患者发生的3级或4级毒性为中性粒细胞减少、皮疹、低钠血症和呕吐。在可评价研究人群中，中位无进展生存期为3.1个月（95% CI：1.5-5.6），中位总生存期为11.9个月（95% CI 9.0-16.9）。GV在转移性葡萄膜黑色素瘤中耐受良好。尽管客观缓解率较低，但疾病控制率为57%。探索性免疫相关性研究正在进行中，以提供对靶点饱和度、组合策略和抗原释放的深入了解。
Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. GPNMB expression was assessed pre- and post-treatment via immunohistochemistry for patients with available tumor tissue. Out of 35 patients who received treatment, two patients had confirmed partial responses (PRs; 6%), and 18 patients had a stable disease (SD; 51%) as the best objective response. 38% of the patients had stable disease >100 days. The grade 3 or 4 toxicities that occurred in two or more patients were neutropenia, rash, hyponatremia, and vomiting. The median progression-free survival was 3.1 months (95% CI: 1.5-5.6), and the median overall survival was 11.9 months (95% CI 9.0-16.9) in the evaluable study population. GV is well-tolerated in metastatic uveal melanoma. The disease control rate was 57% despite a low objective response rate. Exploratory immune correlation studies are underway to provide insight into target saturation, combination strategies, and antigen release.