Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, Washington, DC.
Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
Clin Lung Cancer. 2019 May;20(3):e407-e412. doi: 10.1016/j.cllc.2018.12.022. Epub 2019 Jan 4.
Afatinib is a selective, irreversible ErbB family blocker that has shown survival benefit in lung squamous-cell carcinoma (SCC) patients. Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody to the programmed cell death 1 (PD-1) receptor, has also shown survival benefit in lung SCC. Concurrent inhibition of the PD-1 and epidermal growth factor receptor (EGFR) pathways represents a rational approach to improve responses and delay the onset of treatment resistance in lung SCC.
This phase II, open-label, single-arm study (NCT03157089) is designed to assess the efficacy and safety of afatinib in combination with pembrolizumab in patients with stage IIIB/IV lung SCC that has progressed during/after first-line platinum-based chemotherapy. Eligible patients must have ≥1 target lesion (as per Response Evaluation Criteria in Solid Tumors version 1.1) and must have not received previous immune checkpoint inhibitor/EGFR-targeted therapy. The recommended phase II dose (RP2D) and safety profile will be determined during a safety run-in with oral afatinib (starting dose, 40 mg/d) with intravenous pembrolizumab (200 mg every 3 weeks). In the main study, all patients will receive afatinib at the RP2D with pembrolizumab until disease progression, unacceptable toxicity, or for up to 35 cycles. The primary end point is objective response (complete + partial response). Other end points include disease control, duration of objective response, progression-free survival, overall survival, tumor shrinkage, RP2D, and pharmacokinetics. Exploratory biomarker analysis will be performed. This study is being conducted in the United States, Spain, France, South Korea, and Turkey. Enrollment commenced in September 2017, with a target of 50 to 62 patients.
阿法替尼是一种选择性、不可逆的 ErbB 家族阻滞剂，已显示可延长肺鳞状细胞癌（SCC）患者的生存获益。帕博利珠单抗是一种针对程序性死亡受体 1（PD-1）的人源化 IgG4 单克隆抗体，也已显示可延长肺 SCC 患者的生存获益。同时抑制 PD-1 和表皮生长因子受体（EGFR）通路是一种合理的方法，可以提高反应率并延迟肺 SCC 患者对治疗的耐药性的发生。
这项 II 期、开放标签、单臂研究（NCT03157089）旨在评估阿法替尼联合帕博利珠单抗治疗一线含铂化疗期间/后进展的 IIIB/IV 期肺 SCC 患者的疗效和安全性。符合条件的患者必须有≥1 个靶病灶（根据实体瘤反应评价标准 1.1 版），且未接受过免疫检查点抑制剂/EGFR 靶向治疗。在口服阿法替尼（起始剂量 40 mg/d）联合静脉帕博利珠单抗（每 3 周 200 mg）的安全性入组期间，将确定推荐的 II 期剂量（RP2D）和安全性概况。在主要研究中，所有患者将接受 RP2D 的阿法替尼联合帕博利珠单抗治疗，直至疾病进展、无法耐受的毒性或最多 35 个周期。主要终点是客观缓解（完全缓解+部分缓解）。其他终点包括疾病控制、客观缓解持续时间、无进展生存期、总生存期、肿瘤缩小、RP2D 和药代动力学。将进行探索性生物标志物分析。这项研究正在美国、西班牙、法国、韩国和土耳其进行。2017 年 9 月开始入组，目标入组患者 50 至 62 例。
