Abstract：
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.
摘要：
2022年1月25日，美国食品和药物管理局（FDA）批准使用tebentafusp，双特异性糖蛋白100（gp100）肽-人类白细胞抗原（HLA）定向的CD3T细胞激活剂，用于治疗HLA-A*02：01阳性的不可切除或转移性葡萄膜黑色素瘤（mUM）的成年患者。药效学数据表明tebentafusp靶向特定的HLA-A*02:01/gp100复合物，激活诱导肿瘤细胞死亡的CD4+/CD8+效应和记忆T细胞。Tebentafusp每天或每周通过静脉输注给予患者，取决于指示。III期试验记录了1年的总生存率为73％，总反应率为9%，无进展生存率为31%，疾病控制率为46%。报告的常见不良事件是细胞因子释放综合征，皮疹,发热,瘙痒,疲劳,恶心,发冷,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表现出明显的基因突变，当使用传统的黑色素瘤治疗时，其表型导致有限的生存功效。对mUM的低电流治疗功效，除了不良的长期预后和高死亡率，优先批准tebentafusp在其临床影响方面具有开创性。这篇综述将讨论药效学和药代动力学概况，以及用于评估tebentafusp安全性和有效性的临床试验。
