Dilpacimab (formerly ABT-165), a novel dual-variable domain immunoglobulin, targets both delta-like ligand 4 (DLL4) and VEGF pathways. Here, we present safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy data from a phase I study (trial registration ID: [NCT01946074][1]) of dilpacimab in patients with advanced solid tumors. Eligible patients (≥18 years) received dilpacimab intravenously on days 1 and 15 in 28-day cycles at escalating dose levels (range, 1.25–7.5 mg/kg) until progressive disease or unacceptable toxicity. As of August 2018, 55 patients with solid tumors were enrolled in the dilpacimab monotherapy dose-escalation and dose-expansion cohorts. The most common treatment-related adverse events (TRAE) included hypertension (60.0%), headache (30.9%), and fatigue (21.8%). A TRAE of special interest was gastrointestinal perforation, occurring in 2 patients (3.6%; 1 with ovarian and 1 with prostate cancer) and resulting in 1 death. The PK of dilpacimab showed a half-life ranging from 4.9 to 9.5 days, and biomarker analysis demonstrated that the drug bound to both VEGF and DLL4 targets. The recommended phase II dose for dilpacimab monotherapy was established as 3.75 mg/kg, primarily on the basis of tolerability through multiple cycles. A partial response was achieved in 10.9% of patients (including 4 of 16 patients with ovarian cancer). The remaining patients had either stable disease (52.7%), progressive disease (23.6%), or were deemed unevaluable (12.7%). These results demonstrate that dilpacimab monotherapy has an acceptable safety profile, with clinical activity observed in patients with advanced solid tumors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01946074&atom=%2Fmolcanther%2F20%2F10%2F1988.atom

中文翻译：

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评估地尔帕西单抗在晚期实体瘤患者中的安全性、药代动力学和初步疗效的 I 期开放标签研究

Dilpacimab（以前称为 ABT-165）是一种新型双可变结构域免疫球蛋白，靶向 delta 样配体 4 (DLL4) 和 VEGF 通路。在这里，我们展示了地尔帕西单抗治疗晚期实体瘤患者的 I 期研究（试验注册 ID：[NCT01946074][1]）的安全性、药代动力学 (PK)、药效学 (PD) 和初步疗效数据。符合条件的患者（≥18 岁）在第 1 天和第 15 天以递增的剂量水平（范围 1.25–7.5 mg/kg）在 28 天的周期内静脉接受地尔帕西单抗，直至疾病进展或出现不可接受的毒性。截至 2018 年 8 月，55 名实体瘤患者被纳入地尔帕西单抗单药剂量递增和剂量扩展队列。最常见的治疗相关不良事件 (TRAE) 包括高血压 (60.0%)、头痛 (30.9%) 和疲劳 (21.8%)。特别感兴趣的 TRAE 是胃肠道穿孔，发生在 2 名患者中（3.6%；1 名患有卵巢癌，1 名患有前列腺癌），并导致 1 名患者死亡。dilpacimab 的 PK 显示半衰期为 4.9 至 9.5 天，生物标志物分析表明该药物与 VEGF 和 DLL4 靶标结合。地尔帕西单抗单药治疗的推荐 II 期剂量确定为 3.75 mg/kg，主要基于多个周期的耐受性。10.9% 的患者（包括 16 名卵巢癌患者中的 4 名）实现了部分缓解。其余患者病情稳定 (52.7%)、进行性疾病 (23.6%) 或被认为无法评估 (12.7%)。这些结果表明，地尔帕西单抗单一疗法具有可接受的安全性，在晚期实体瘤患者中观察到临床活性。