Abstract：
MET amplification (METamp), a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors, occurs in up to 30% of patients with non-small-cell lung cancer (NSCLC) progressing on first-line osimertinib. Combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor, may overcome METamp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic EGFR-mutant NSCLC and acquired resistance to first-line osimertinib and METamp, determined centrally by fluorescence in situ hybridization (gene copy number ≥5 and/or MET/CEP7 ≥2) at time of progression. Patients will receive tepotinib 500 mg (450 mg active moiety) plus osimertinib 80 mg once-a-day. The primary end point is objective response, and secondary end points include duration of response, progression-free survival, overall survival and safety. Trial registration number: NCT03940703 (clinicaltrials.gov).
Osimertinib is used to treat a type of lung cancer that has specific changes (mutations) in a gene called EGFR. Although tumors will usually shrink (respond) during treatment with osimertinib, they can stop responding, or become resistant, to osimertinib. A common cause of resistance is ‘MET amplification’, which describes when extra copies of a gene called MET are present. Lung cancer that is resistant to osimertinib due to MET amplification could be treated by combining osimertinib with a treatment that blocks MET, such as tepotinib. INSIGHT 2 is an ongoing study that is designed to learn about the effects and safety of tepotinib combined with osimertinib, in patients with lung cancer that has stopped responding to osimertinib because of MET amplification. A plain language version of this article is available and is published alongside the paper online: www.futuremedicine.com/doi/suppl/10.2217/fon-2021-1406.
Osimertinib is used to treat a type of lung cancer that has specific changes (mutations) in a gene called EGFR. Although tumors will usually shrink (respond) during treatment with osimertinib, they can stop responding, or become resistant, to osimertinib. A common cause of resistance is ‘MET amplification’, which describes when extra copies of a gene called MET are present. Lung cancer that is resistant to osimertinib due to MET amplification could be treated by combining osimertinib with a treatment that blocks MET, such as tepotinib. INSIGHT 2 is an ongoing study that is designed to learn about the effects and safety of tepotinib combined with osimertinib, in patients with lung cancer that has stopped responding to osimertinib because of MET amplification. A plain language version of this article is available and is published alongside the paper online: www.futuremedicine.com/doi/suppl/10.2217/fon-2021-1406.
摘要：
MET扩增(METamp),对EGFR酪氨酸激酶抑制剂的获得性耐药机制，在一线奥希替尼进展的非小细胞肺癌(NSCLC)患者中,有高达30%的患者发生.奥希替尼与MET抑制剂联合使用，如替泊替尼，一个口头，高度选择性,有效的MET酪氨酸激酶抑制剂，可以克服METamp驱动的阻力。观察2号(NCT03940703),一个国际,开放标签，多中心II期试验，评估特泊替尼联合奥希替尼治疗晚期/转移性EGFR突变型非小细胞肺癌和一线奥希替尼和METamp获得性耐药患者的疗效,在进展时通过荧光原位杂交（基因拷贝数≥5和/或MET/CEP7≥2）集中确定。患者将每天一次接受托泊替尼500mg（450mg活性部分）加奥希替尼80mg。主要终点是客观反应，次要终点包括反应持续时间，无进展生存期,总体生存率和安全性。试验注册号：NCT03940703（clinicaltrials.gov）。
奥希替尼用于治疗一种在称为EGFR的基因中具有特定变化（突变）的肺癌。尽管奥希替尼治疗期间肿瘤通常会缩小（反应），他们可以停止回应，或者变得有抵抗力，奥希替尼。抵抗的常见原因是“MET扩增”，它描述了一个叫做MET的基因的额外拷贝何时存在。由于MET扩增而对奥希替尼耐药的肺癌可以通过将奥希替尼与阻断MET的治疗相结合来治疗，如替泊替尼。INSIGHT2是一项正在进行的研究，旨在了解特泊替尼联合奥希替尼的疗效和安全性。在由于MET扩增而对奥希替尼停止反应的肺癌患者中。本文的简单语言版本可用，并与在线论文一起发布：www。未来医学.com/doi/suppl/10.2217/fon-2021-1406。
奥希替尼用于治疗一种在称为EGFR的基因中具有特定变化（突变）的肺癌。尽管奥希替尼治疗期间肿瘤通常会缩小（反应），他们可以停止回应，或者变得有抵抗力，奥希替尼。抵抗的常见原因是“MET扩增”，它描述了一个叫做MET的基因的额外拷贝何时存在。由于MET扩增而对奥希替尼耐药的肺癌可以通过将奥希替尼与阻断MET的治疗相结合来治疗，如替泊替尼。INSIGHT2是一项正在进行的研究，旨在了解特泊替尼联合奥希替尼的疗效和安全性。在由于MET扩增而对奥希替尼停止反应的肺癌患者中。本文的简单语言版本可用，并与在线论文一起发布：www。未来医学.com/doi/suppl/10.2217/fon-2021-1406。
