Bintrafusp alfa, a first‐in‐class bifunctional fusion protein composed of the extracellular domain of the TGF‐βRII receptor (TGF‐β “trap”) fused to a human IgG1‐blocking PD‐L1, showed a manageable safety profile and clinical activity in phase I studies in patients with heavily pretreated advanced solid tumors. The recommended phase 2 dose (RP2D) was selected based on integration of modeling, simulations, and all available data. A 1,200‐mg every 2 weeks (q2w) dose was predicted to maintain serum trough concentration (C_trough) that inhibits all targets of bintrafusp alfa in circulation in > 95% of patients, and a 2,400‐mg every 3 weeks (q3w) dose was predicted to have similar C_trough. A trend toward an association between exposure and efficacy variables and a relatively stronger inverse association between clearance and efficacy variables were observed. Exposure was either weakly or not correlated with probability of adverse events. The selected intravenous RP2D of bintrafusp alfa is 1,200 mg q2w or 2,400 mg q3w.

中文翻译：

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为Bintrafusp Alfa（一种针对TGF-β和PD-L1的双功能融合蛋白）推荐的2期推荐剂量。

Bintrafusp alfa是一种一流的双功能融合蛋白，由与人IgG1阻断性PD-L1融合的TGF-βRII受体的胞外域（TGF-β“陷阱”）组成，具有可控的安全性和临床活性在经过大量预处理的晚期实体瘤患者的I期研究中。基于建模，仿真和所有可用数据的集成，选择了推荐的2期剂量（RP2D）。预计每2周（q2w）剂量为1200 mg，可维持超过95％的患者的血清谷浓度（C _trough），从而抑制Bintrafusp alfa循环中的所有靶标，每3周（q3w）剂量为2,400-mg预计有相似的C_谷。观察到暴露与功效变量之间有关联的趋势，以及清除率与功效变量之间有相对较强的逆相关性。暴露与不良事件的可能性微弱或无关。Bintrafusp alfa的选定静脉RP2D为1,200 mg q2w或2,400 mg q3w。