PURPOSE To evaluate the safety, pharmacokinetics, and preliminary activity of bemarituzumab in patients with FGFR2b-overexpressing gastric and gastroesophageal junction adenocarcinoma (GEA). PATIENTS AND METHODS FPA144-001 was a phase I, open-label, multicenter trial consisting of the following 3 parts: part 1a involved dose escalation in patients with recurrent solid tumors at doses ranging from 0.3 to 15 mg/kg; part 1b involved dose escalation in patients with advanced-stage GEA; and part 2 involved dose expansion in patients with advanced-stage GEA that overexpressed FGFR2b at various levels (4 cohorts; high, medium, low, and no FGFR2b overexpression) and 1 cohort of patients with FGFR2b-overexpressing advanced-stage bladder cancer. RESULTS Seventy-nine patients were enrolled; 19 were enrolled in part 1a, 8 in part 1b, and 52 in part 2. No dose-limiting toxicities were reported, and the recommended dose was identified as 15 mg/kg every 2 weeks based on safety, tolerability, pharmacokinetic parameters, and clinical activity. The most frequent treatment-related adverse events (TRAEs) were fatigue (17.7%), nausea (11.4%), and dry eye (10.1%). Grade 3 TRAEs included nausea (2 patients) and anemia, neutropenia, increased AST, increased alkaline phosphatase, vomiting, and an infusion reaction (1 patient each). Three (10.7%) of 28 patients assigned to a cohort receiving a dose of ≥ 10 mg/kg every 2 weeks for ≥ 70 days reported reversible grade 2 corneal TRAEs. No TRAEs of grade ≥ 4 were reported. Five (17.9%; 95% CI, 6.1% to 36.9%) of 28 patients with high FGFR2b-overexpressing GEA had a confirmed partial response. CONCLUSION Overall, bemarituzumab seems to be well tolerated and demonstrated single-agent activity as late-line therapy in patients with advanced-stage GEA. Bemarituzumab is currently being evaluated in combination with chemotherapy in a phase III trial as front-line therapy for patients with high FGFR2b-overexpressing advanced-stage GEA.

中文翻译：

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Bemarituzumab (FPA144) 在晚期实体瘤和 FGFR2b 选择的胃食管腺癌患者中的 I 期升级和扩展研究

目的评估 bemarituzumab 在 FGFR2b 过表达的胃和胃食管交界处腺癌 (GEA) 患者中的安全性、药代动力学和初步活性。患者和方法 FPA144-001 是一项 I 期、开放标签、多中心试验，由以下 3 个部分组成：第 1a 部分涉及复发性实体瘤患者的剂量递增，剂量范围为 0.3 至 15 mg/kg；第 1b 部分涉及晚期 GEA 患者的剂量递增；第 2 部分涉及在不同水平过表达 FGFR2b 的晚期 GEA 患者（4 组；高、中、低和无 FGFR2b 过表达）和 1 组 FGFR2b 过表达晚期膀胱癌患者的剂量扩展。结果 共纳入 79 名患者；19 人参加了第 1a 部分，8 人参加了第 1b 部分，52 人参加了第 2 部分。没有报告剂量限制性毒性，根据安全性、耐受性、药代动力学参数和临床活性，推荐剂量确定为每 2 周 15 mg/kg。最常见的治疗相关不良事件 (TRAE) 是疲劳 (17.7%)、恶心 (11.4%) 和干眼 (10.1%)。3 级 TRAE 包括恶心（2 名患者）和贫血、中性粒细胞减少、AST 增加、碱性磷酸酶增加、呕吐和输液反应（各 1 名患者）。每 2 周接受 ≥ 10 mg/kg 剂量治疗≥ 70 天的队列中的 28 名患者中有 3 名 (10.7%) 报告了可逆的 2 级角膜 TRAE。没有报告 ≥ 4 级的 TRAE。28 名 FGFR2b 高过表达 GEA 患者中有 5 名（17.9%；95% CI，6.1% 至 36.9%）得到确认的部分缓解。结论 总的来说，bemarituzumab 似乎具有良好的耐受性，并在晚期 GEA 患者中证明了单药活性作为晚期治疗。Bemarituzumab 目前正在 III 期试验中与化疗联合进行评估，作为 FGFR2b 高表达晚期 GEA 患者的一线治疗。