Tebentafusp:一种治疗转移性葡萄膜黑色素瘤的新药。

Pub Date : 2023-03-01 DOI:10.1358/dot.2023.59.3.3542417
Zhijian Wang, Yuhao Xie, Jing-Quan Wang, Yuanhui Cheng, Joshua Fleishman, Zhe-Sheng Chen, Yun Chen
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引用次数: 2

摘要

2022年1月25日,美国食品和药物管理局(FDA)批准使用tebentafusp,一种双特异性糖蛋白100 (gp100)肽-人白细胞抗原(HLA)定向CD3 t细胞激活剂,用于治疗HLA- a *02:01阳性的成人不可切除或转移性葡萄膜黑色素瘤(mUM)患者。药效学数据表明,tebentafusp靶向特异性HLA-A*02:01/gp100复合体,激活CD4+/CD8+效应细胞和记忆T细胞,诱导肿瘤细胞死亡。Tebentafusp每天或每周通过静脉输注给患者,取决于适应症。III期临床试验表明,1年总生存率为73%,总缓解率为9%,无进展生存率为31%,疾病控制率为46%。常见的不良事件有细胞因子释放综合征、皮疹、发热、瘙痒、疲劳、恶心、寒战、腹痛、水肿、低血压、皮肤干燥、头痛和呕吐。与其他类型的黑色素瘤相比,mUM呈现出独特的基因突变特征,这在使用传统黑色素瘤治疗时显着导致有限的生存疗效。目前对mUM的治疗效果较低,加上长期预后差和死亡率高,使得tebentafusp的批准具有开创性的临床影响。本文将讨论替本他福的药效学和药代动力学特征,以及用于评价其安全性和有效性的临床试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tebentafusp: a novel drug for the treatment of metastatic uveal melanoma.

On January 25, 2022, the U.S. Food and Drug Administration (FDA) approved the use of tebentafusp, a bispecific glycoprotein 100 (gp100) peptide-human leukocyte antigen (HLA)-directed CD3 T-cell activator, for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Pharmacodynamic data indicate that tebentafusp targets a specific HLA-A*02:01/gp100 complex, activating both CD4+/CD8+ effector and memory T cells that induce tumor cell death. Tebentafusp is administered to patients via intravenous infusion daily or weekly, depending on the indication. Phase III trials have documented a 1-year overall survival of 73%, overall response rate of 9%, progression-free survival of 31% and disease control rate of 46%. Common adverse events reported are cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache and vomiting. Compared to other types of melanomas, mUM presents with a distinct profile of genetic mutations, which phenotypically results in limited survival efficacy when using traditional melanoma treatments. The low current treatment efficacy for mUM, alongside a poor long-term prognosis and high mortality rates, gives precedence for the approval of tebentafusp to be groundbreaking in its clinical impact. This review will discuss the pharmacodynamic and pharmacokinetic profile, and the clinical trials used to evaluate the safety and efficacy of tebentafusp.

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