Rodon J, Rothe M, Mangat P K, Garrett-Mayer E, Cannon T L, Hobbs E, Kalemkerian G P, Hinshaw D C, Gregory A, Grantham G N, Halabi S, Schilsky R L
Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, USA.
American Society of Clinical Oncology, Alexandria, USA.
ESMO Open. 2025 Apr 10;10(5):104545. doi: 10.1016/j.esmoop.2025.104545.
TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Results of four patients with various tumors with NRG1 fusions treated with afatinib are reported.
Eligible patients had advanced cancer, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with NRG1 fusions, and no standard treatment options. The primary endpoint was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks' duration (SD16+). Secondary endpoints included OR, duration of response, duration of SD, and safety.
Four patients were enrolled from February 2020 to July 2021; all had solid tumors [colorectal cancer (n = 2), non-small-cell lung cancer (n = 1), and pancreatic adenocarcinoma (n = 1)] with an NRG1 fusion. All patients were evaluable for efficacy. One partial response and two SD16+ were observed. One patient was still alive as of October 2024 with SD of 134 weeks' duration. No patients had a drug-related grade 3-5 adverse event (AE) or serious AE.
Though the sample size was small, afatinib demonstrated promising activity in patients with advanced solid tumors with NRG1 fusions, including durable DC warranting additional study.
TAPUR是一项II期篮子试验，评估市售靶向药物在晚期癌症且具有可靶向基因组改变患者中的抗肿瘤活性。报告了4例接受阿法替尼治疗的患有NRG1融合的各种肿瘤患者的结果。
符合条件的患者患有晚期癌症、可测量疾病（RECIST标准）、东部肿瘤协作组体能状态0 - 2、器官功能良好、具有NRG1融合的肿瘤且无标准治疗方案。主要终点为疾病控制（DC），定义为客观缓解（OR）或至少持续16周的疾病稳定（SD）（SD16+）。次要终点包括OR、缓解持续时间、SD持续时间和安全性。
2020年2月至2021年7月共纳入4例患者；均患有实体瘤[结直肠癌（n = 2）、非小细胞肺癌（n = 1）和胰腺腺癌（n = 1）]且具有NRG1融合。所有患者均可评估疗效。观察到1例部分缓解和2例SD16+。截至2024年10月，1例患者仍存活，SD持续时间为134周。无患者发生与药物相关的3 - 5级不良事件（AE）或严重AE。
尽管样本量较小，但阿法替尼在具有NRG1融合的晚期实体瘤患者中显示出有前景的活性，包括持久的疾病控制，值得进一步研究。
