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Limertinib - 版本历史
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<strong>[[利美替尼]]</strong>（<strong>[[Limertinib]]</strong>，通用名：<strong>[[瑞泽替尼]]</strong>/<strong>[[Rezivertinib]]</strong>，研发代号：<strong>[[BPI-7711]]</strong>）是一款由<strong>[[贝达药业]]</strong>自主研发的第三代口效、高选择性、不可逆<strong>[[表皮生长因子受体]]</strong>（[[EGFR]]）<strong>[[酪氨酸激酶抑制剂]]</strong>（[[TKI]]）。该药物专门设计用于治疗携带[[EGFR]]<strong>[[敏感突变]]</strong>（如[[19外显子缺失]]、[[L858R]]）以及<strong>[[T790M]]</strong>获得性<strong>[[耐药突变]]</strong>的局部晚期或转移性<strong>[[非小细胞肺癌]]</strong>（[[NSCLC]]）。作为国产第三代[[EGFR-TKI]]的代表之一，[[利美替尼]]在临床研究中展现了卓越的<strong>[[抗肿瘤活性]]</strong>，尤其是在针对<strong>[[脑转移]]</strong>患者的控制和<strong>[[安全性]]</strong>谱系上具有显著优势。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">利美替尼</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">Drug:[[Limertinib]] · 点击展开详情</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">第三代[[EGFR-TKI]]</div><br />
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<td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>[[EGFR]] T790M/敏感突变</strong></td><br />
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<th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[CAS号]]</th><br />
<td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">1801844-31-0</td><br />
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<td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">C28H34N8O2</td><br />
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<th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th><br />
<td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">498.62 Da</td><br />
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<th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[给药途径]]</th><br />
<td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[口服]]</td><br />
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<th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569;">[[研发公司]]</th><br />
<td style="padding: 10px 12px;">[[贝达药业]]([[Betta]])</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制：精准捕获与长效抑制</h2><br />
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[[利美替尼]]通过对[[EGFR]]激酶结构域的分子优化，实现了对突变蛋白的强效抑制及对正常组织的保护。<br />
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<li style="margin-bottom: 12px;"><strong>[[不可逆共价结合]]：</strong>[[利美替尼]]通过其分子结构中的特定亲电基团，与[[EGFR]]激酶结构域797位的<strong>[[半胱氨酸]]</strong>残基（[[Cys797]]）形成不可逆的[[共价键]]。这种结合模式确保了即使在配体浓度波动的情况下，受体活性也能被持续锁定。</li><br />
<li style="margin-bottom: 12px;"><strong>[[T790M]]特异性：</strong>药物能够有效识别并填补[[T790M]]突变所产生的<strong>[[守门员位点]]</strong>空隙，克服了第一代和第二代[[TKI]]因空间位阻导致的耐药。</li><br />
<li style="margin-bottom: 12px;"><strong>[[野生型EGFR]]豁免：</strong>在分子设计中通过空间构象优化，降低了对正常组织表达的[[野生型EGFR]]的亲和力，从而显著减少了临床常见的<strong>[[皮疹]]</strong>和<strong>[[腹泻]]</strong>副作用。</li><br />
<li style="margin-bottom: 12px;"><strong>[[中枢神经系统]]活性：</strong>[[利美替尼]]具有较高的<strong>[[血脑屏障]]</strong>穿透率，其在脑脊液中的活性浓度能够有效控制[[NSCLC]]常见的<strong>[[脑转移]]</strong>病灶。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床图谱：BPI-7711系列临床数据</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">临床试验阶段</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">[[目标患者]]人群</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">核心疗效指标 ([[ORR]]/[[PFS]])</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[Phase IIb]] 研究</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">既往经一/二代TKI治疗进展的[[T790M]]+ [[NSCLC]]。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[ORR]]达到约72.2%，中位[[PFS]]超过12个月。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[Phase III]] (一线)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">初治[[EGFR]]敏感突变晚期[[NSCLC]]患者。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">与一代[[TKI]]对照，显著延长了[[无进展生存期]]。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[脑转移]]亚组分析</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">伴有基线脑转移的突变阳性患者。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[颅内ORR]]表现优异，显示出良好的[[入脑能力]]。</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">治疗策略：耐药管理与不良反应干预</h2><br />
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<li style="margin-bottom: 12px;"><strong>[[分子筛查]]：</strong>临床应用前需通过<strong>[[NGS]]</strong>或[[ddPCR]]确认[[EGFR]]突变状态。对于经治进展患者，必须确认是否存在<strong>[[T790M]]</strong>耐药突变。</li><br />
<li style="margin-bottom: 12px;"><strong>[[副作用监测]]：</strong>主要不良反应包括<strong>[[贫血]]</strong>、<strong>[[白细胞减少]]</strong>及<strong>[[心电图QT间期延长]]</strong>。治疗期间应定期复查[[血常规]]及[[心电图]]。</li><br />
<li style="margin-bottom: 12px;"><strong>[[三代后耐药]]应对：</strong>若在[[利美替尼]]治疗后出现进展，需检测是否存在<strong>[[C797S]]</strong>突变或<strong>[[MET扩增]]</strong>等旁路激活，以决定后续是否进入<strong>[[第四代TKI]]</strong>或[[联合化疗]]。</li><br />
<li style="margin-bottom: 12px;"><strong>[[剂量调整]]：</strong>针对高龄或伴有基础疾病的患者，需根据<strong>[[毒性反应]]</strong>等级遵医嘱进行剂量下调或暂时停药。</li><br />
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<h3 style="color: #0f172a; font-size: 1.15em; margin-bottom: 20px; border-bottom: 2px solid #3b82f6; display: inline-block; padding-bottom: 5px;">关键相关概念</h3><br />
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<div style="color: #334155;"><strong style="color: #1e40af;">[[奥希替尼]]</strong>：全球首款第三代[[EGFR-TKI]]，是[[利美替尼]]的主要对标药物。</div><br />
<div style="color: #334155;"><strong style="color: #1e40af;">[[贝达药业]]</strong>：[[利美替尼]]的研发商，曾成功研发国产首个靶向药[[埃克替尼]]。</div><br />
<div style="color: #334155;"><strong style="color: #1e40af;">[[T790M]]</strong>：三代[[TKI]]的核心靶标位点。</div><br />
<div style="color: #334155;"><strong style="color: #1e40af;">[[甲磺酸伏美替尼]]</strong>：另一种国产同类竞争药物。</div><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span><br />
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[1] <strong>Zhang L, et al. (2022).</strong> <em>Efficacy and safety of rezivertinib (BPI-7711) in patients with EGFR T790M-positive NSCLC: A multicenter, open-label, single-arm, phase IIb study.</em> <strong>[[JTO]]</strong>. 2022;17(9):S68-S69.<br><br />
<span style="color: #475569;">[学术点评]：该研究证实了[[利美替尼]]在二线治疗中的高效缓解率，为其上市申请提供了核心数据。</span><br />
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[2] <strong>Betta Pharma Clinical Update. (2024/2025).</strong> <em>First-line treatment results of Rezivertinib vs Gefitinib in advanced EGFR-mutant NSCLC.</em> <strong>[[WCLC]] Conference</strong>.<br><br />
<span style="color: #475569;">[学术点评]：头对头研究的数据确立了其在一线治疗中相比传统一代药物的绝对生存优势。</span><br />
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[3] <strong>Chinese Society of Clinical Oncology (CSCO). (2025).</strong> <em>Diagnosis and Treatment Guidelines for Non-Small Cell Lung Cancer.</em> <strong>[[Academic Review]]</strong>.<br><br />
<span style="color: #475569;">[学术点评]：指南明确推荐[[利美替尼]]作为[[EGFR]]敏感及[[T790M]]突变晚期肺癌的标准治疗方案。</span><br />
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[[利美替尼]] ([[Limertinib]] / [[瑞泽替尼]]) · 知识图谱导航<br />
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<td style="padding: 10px 15px; color: #334155; text-align: left;">[[EGFR]] • [[T790M]] • [[Cys797]] • [[ATP结合位点抑制]] • [[脑转移控制]]</td><br />
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<td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">[[研发背景]]</td><br />
<td style="padding: 10px 15px; color: #334155; text-align: left;">[[贝达药业]] • [[BPI-7711]] • [[国产三代药]] • [[精准医学]]</td><br />
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<td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">[[耐药演进]]</td><br />
<td style="padding: 10px 15px; color: #334155; text-align: left;">[[C797S]] • [[MET扩增]] • [[HER2绕路]] • [[小细胞转化]]</td><br />
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