This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose escalation (3+3 design), 3 to 6 patients with advanced solid tumors were enrolled into four dose cohorts (5–25 mg/kg). In the dose-expansion phase, a subset of patients was prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every 21 days. For dose expansion, 15 mg/kg was chosen as the dose on the basis of safety, pharmacokinetics, and other data from the escalation cohorts. Forty-five patients were enrolled and received at least one dose of telisotuzumab (dose escalation, n = 15; dose expansion, n = 30). Telisotuzumab showed a linear pharmacokinetics profile; peak plasma concentration was proportional to dose level. There were no acute infusion reactions and no dose-limiting toxicities were observed. The most common treatment-related adverse events included hypoalbuminemia (n = 9, 20.0%) and fatigue (n = 5, 11.1%). By Response Evaluation Criteria In Solid Tumors (RECIST), 4 of 10 (40.0%) patients with MET-amplified tumors had confirmed partial response in target lesions (one ovarian, two gastric, and one esophageal), two (20.0%) had stable disease, three (30.0%) had progressive disease; one patient was unable to be evaluated. Among patients with nonamplified tumors (n = 35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria. In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors.

中文翻译：

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Telisotuzumab (ABT-700)（一种抗 c-Met 抗体）在晚期实体瘤患者中的 1 期剂量递增和扩展研究

这项首次人体 I 期研究评估了 telisotuzumab（以前称为 ABT-700，一种针对 c-Met 的拮抗性抗体）的药代动力学、安全性和初步疗效。对于剂量递增（3+3 设计），将 3 至 6 名晚期实体瘤患者纳入四个剂量队列（5-25 mg/kg）。在剂量扩展阶段，前瞻性选择一部分患者进行 MET 扩增（FISH 筛查）。患者每 21 天在第 1 天静脉注射 telisotuzumab。对于剂量扩展，根据安全性、药代动力学和来自递增队列的其他数据，选择 15 mg/kg 作为剂量。45 名患者入组并接受了至少一剂 telisotuzumab（剂量递增，n = 15；剂量扩展，n = 30）。Telisotuzumab 显示线性药代动力学特征；峰值血浆浓度与剂量水平成正比。没有急性输液反应，也没有观察到剂量限制性毒性。最常见的治疗相关不良事件包括低白蛋白血症 (n = 9, 20.0%) 和疲劳 (n = 5, 11.1%)。根据实体瘤反应评估标准 (RECIST)，10 名 MET 扩增肿瘤患者中有 4 名 (40.0%) 在目标病变（1 个卵巢、2 个胃和 1 个食管）中确认了部分反应，2 个 (20.0%) 具有稳定疾病，三个（30.0%）有进行性疾病；一名患者无法评估。在未扩增肿瘤患者（n = 35）中，未观察到客观反应；然而，根据 RECIST 标准，11 名患者病情稳定。综上所述，