Silevertinib

The outlook for the EGFR inhibitor market continues to be highly promising, supported by the increasing adoption of precision medicine in oncology and the broader use of targeted therapies across various cancer indications. Additionally, the expected launch of therapies such as Zipalertinib (CLN-081) (Cullinan Oncology/Taiho Pharma), Firmonertinib (ArriVent BioPharma), Ivonescimab (SMT112) (Akeso Biopharma/Summit Therapeutics), PF-08046054 (Pfizer), Patritumab Deruxtecan (Daiichi Sankyo/AstraZeneca), and others will further propel the market growth. LAS VEGAS, June 15, 2026 /PRNewswire/ -- DelveInsight's EGFR Inhibitors Market Size, Target Population, Competitive Landscape & Market Forecast report includes a comprehensive understanding of current treatment practices, addressable patient population, which includes top indications such as Non-small cell lung cancer (NSCLC), Colorectal cancer (CRC), Head and neck cancer (HNC), and others. The selected indications are based on approved therapies and ongoing pipeline activity. The report also provides insights into the emerging EGFR inhibitors, market share of individual therapies, and current and forecasted market size from 2022 to 2036, segmented into leading markets (the US, EU4, UK, and Japan). Key Takeaways from the EGFR Inhibitors Market Report The market size for EGFR inhibitors was found to be USD 7 billion in the 7MM in 2025. The United States accounted for the largest EGFR inhibitor treatment market size, approximately 60% of the total market size in the 7MM in 2025, compared to other major markets, including the EU4 countries (Germany, France, Italy, and Spain), the United Kingdom, and Japan. The report provides the total potential number of patients in the indications, such as Non-small cell lung cancer (NSCLC), Colorectal cancer (CRC), Head and neck cancer (HNC), and others. In 2025, the 7MM had approximately ~330,000 incident cases of EGFR Inhibitors. Leading EGFR inhibitor companies, such as Cullinan Oncology, Taiho Pharma, ArriVent BioPharma, Akeso Biopharma, Summit Therapeutics, Pfizer, Daiichi Sankyo, AstraZeneca, Merck, Kelun-Biotech, CSPC Pharmaceutical, Shanghai JMT-Bio, Bristol-Myers Squibb, AbbVie, Lantern Pharma, Wayshine Biopharm, Teligene US, Genprex, J Ints Bio, Black Diamond Therapeutics, BlossomHill Therapeutics, Scorpion Therapeutics, Pierre Fabre, Antares Therapeutics, A2 Biotherapeutics, BioNTech, Dragonfly Therapeutics, Merus, DualityBio, ORIC Pharmaceuticals, BeOne Medicines (formerly BeiGene), and others, are developing novel EGFR inhibitors that can be available in the EGFR inhibitors market in the coming years. Some of the key EGFR inhibitors in clinical trials include Zipalertinib (CLN-081), Firmonertinib, Ivonescimab (SMT112), PF-08046054, Patritumab Deruxtecan, Sacituzumab Tirumotecan, (MK-2870), SYS6010, JMT101, Izalontamab Brengitecan (BMS-986507), Telisotuzumab Adizutecan (Temab-A/ABB-400), LP-300, WSD0922-FU, Sutetinib, Quaratusugene ozeplasmid (REQORSA), JIN-A02, Silevertinib, (BDTX-1535), BH-30643, STX-241/PFL-241, STX-721/PFL-271, A2B395, BNT326 (YL 202), DF9001, Pamvatamig (MCLA-129), TAS3351, DB-1310, Enozertinib (ORIC-114 ), BG-60366, and others. In 2036, among all the therapies for EGFR NSCLC, the highest revenue is estimated to be generated by amivantamab (RYBREVANT) ± lazertinib (LAZCLUZE), followed by osimertinib (TAGRISSO), in the US. Discover which EGFR drugs will lose patent exclusivity @ Key Factors Driving the EGFR Inhibitors Market Rising Prevalence of Cancer: Increasing incidence of non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, and head & neck cancers is driving demand for targeted therapies. The growing global cancer burden is expanding the patient pool eligible for EGFR-targeted treatment. Advancements in Precision Medicine: Greater adoption of biomarker-based treatment approaches is supporting the use of EGFR inhibitors in mutation-specific patient populations. Routine molecular testing for EGFR mutations has improved patient identification and treatment selection. Growth in Combination Therapy Approaches: Increasing use of EGFR inhibitors in combination with immunotherapies, chemotherapy, and anti-angiogenic agents is improving clinical outcomes. Combination regimens are helping overcome resistance mechanisms and extending treatment duration. Strong Pipeline and Ongoing Clinical Research: The emerging landscape holds a diverse range of therapeutic alternatives for treatment, including Zipalertinib (CLN-081) (Cullinan Oncology/Taiho Pharma), Firmonertinib (ArriVent BioPharma), Ivonescimab (SMT112) (Akeso Biopharma/Summit Therapeutics), PF-08046054 (Pfizer), Patritumab Deruxtecan (Daiichi Sankyo/AstraZeneca), Sacituzumab Tirumotecan (MK-2870) (Merck/Kelun-Biotech), SYS6010 (CSPC Pharmaceutical), JMT101 (Shanghai JMT-Bio), Izalontamab Brengitecan (BMS-986507) (Bristol-Myers Squibb), Telisotuzumab Adizutecan (Temab-A/ABB-400) (AbbVie), LP-300 (Lantern Pharma), WSD0922-FU (Wayshine Biopharm), Sutetinib (Teligene US), Quaratusugene ozeplasmid (REQORSA) (Genprex), JIN-A02 J (Ints Bio), Silevertinib (BDTX-1535) (Black Diamond Therapeutics), BH-30643 (BlossomHill Therapeutics), STX-241/PFL-241 (Scorpion Therapeutics/Pierre Fabre), STX-721/PFL-271 (Antares Therapeutics), A2B395 (A2 Biotherapeutics), BNT326 (YL 202) (BioNTech), DF9001 (Dragonfly Therapeutics), Pamvatamig (MCLA-129) (Merus), TAS3351 (Taiho Oncology), DB-1310 (DualityBio), Enozertinib (ORIC-114) (ORIC Pharmaceuticals), BG-60366 (BeOne Medicines), and others. The expected launch of these therapies shall further create a positive impact on the market. Aparna Thakur, an oncology expert at DelveInsight, said that Exon 20 insertion has emerged as a key competitive arena, with the approvals of RYBREVANT and ZEGFROVY creating a new market segment, while several late-stage candidates, including furmonertinib and zipalertinib, are further heightening the competitive landscape. EGFR Inhibitors Market Analysis Treatment approaches for EGFR-mutated NSCLC have advanced significantly over the last two decades with the development of targeted EGFR tyrosine kinase inhibitors (TKIs). First-generation agents such as erlotinib and gefitinib, followed by second-generation therapies including afatinib and dacomitinib, and later the third-generation TKI osimertinib, have consistently demonstrated improved clinical outcomes over conventional chemotherapy in terms of response rates and survival. Osimertinib additionally addresses the T790M resistance mutation, although acquired resistance continues to limit long-term efficacy, leaving post-TKI treatment strategies an ongoing clinical challenge. Currently, osimertinib continues to serve as the global standard of care for EGFR-mutant NSCLC, supported by robust progression-free survival (PFS) and overall survival (OS) benefits along with extensive regulatory approvals across multiple disease stages. At the same time, amivantamab is emerging as a strong competitor, broadening its role beyond EGFR exon 20 insertion mutations through combination approaches involving lazertinib and chemotherapy. Competitive intensity within the market is increasing with the arrival of newer therapies such as datopotamab deruxtecan, sunvozertinib, and aumolertinib. Real-world evidence from the 7MM highlights the continued dominance of EGFR TKIs in treatment practice, particularly the widespread frontline adoption of osimertinib, while chemotherapy and immunotherapy continue to play roles in later-line settings and in patients harboring uncommon mutations such as exon 20 insertions. Cetuximab (ERBITUX), an anti-EGFR IgG1 monoclonal antibody, is projected to retain a steady but mature market presence in metastatic colorectal cancer (mCRC) and head and neck cancers. Its position is reinforced by extensive clinical experience, a well-established efficacy profile, and approvals from major regulatory agencies, including the U.S. FDA, EMA, and PMDA. In mCRC, cetuximab remains especially relevant in biomarker-driven settings, particularly among patients with EGFR-expressing and RAS wild-type tumors. Its utility is further strengthened through combination regimens with targeted agents such as encorafenib for BRAF V600E-mutated disease and adagrasib for KRAS G12C-mutated tumors. In head and neck cancers, cetuximab continues to see stable use in combination therapies and among patients who are unsuitable for certain systemic or immunotherapy-based approaches. Nevertheless, despite sustained clinical utilization across key markets, market expansion is expected to be moderate owing to product maturity, biosimilar competition, and the growing adoption of newer targeted therapies and immuno-oncology treatments. EGFR exon 20 insertion-positive NSCLC remains particularly challenging to manage with conventional TKIs. Following the withdrawal of mobocertinib, amivantamab became the primary approved therapeutic option in this segment. However, the approval of sunvozertinib in 2025 has intensified competition, while additional TKIs such as furmonertinib and zipalertinib continue to advance through clinical development. The emergence of ADCs such as PF-08046054 (Pfizer), Patritumab Deruxtecan (Daiichi Sankyo/AstraZeneca), Sacituzumab Tirumotecan (MK-2870) (Merck/Kelun-Biotech), SYS6010 (CSPC Pharmaceutical), Izalontamab Brengitecan (BMS-986507) (Bristol-Myers Squibb), Telisotuzumab Adizutecan (Temab-A/ABB-400) (AbbVie), and others, and next-generation targeted therapies is further reshaping and intensifying the competitive dynamics within the EGFR NSCLC treatment landscape. Learn more about the fastest growing EGFR inhibitor market @ EGFR Inhibitors Analysis EGFR Inhibitors Competitive Landscape Some of the emerging EGFR inhibitors in the clinical trial landscape include Zipalertinib (CLN-081) (Cullinan Oncology/Taiho Pharma), Firmonertinib (ArriVent BioPharma), Ivonescimab (SMT112) (Akeso Biopharma/Summit Therapeutics), PF-08046054 (Pfizer), Patritumab Deruxtecan (Daiichi Sankyo/AstraZeneca), Sacituzumab Tirumotecan (MK-2870) (Merck/Kelun-Biotech), SYS6010 (CSPC Pharmaceutical), JMT101 (Shanghai JMT-Bio), Izalontamab Brengitecan (BMS-986507) (Bristol-Myers Squibb), Telisotuzumab Adizutecan (Temab-A/ABB-400) (AbbVie), LP-300 (Lantern Pharma), WSD0922-FU (Wayshine Biopharm), Sutetinib (Teligene US), Quaratusugene ozeplasmid (REQORSA) (Genprex), JIN-A02 J (Ints Bio), Silevertinib (BDTX-1535) (Black Diamond Therapeutics), BH-30643 (BlossomHill Therapeutics), STX-241/PFL-241 (Scorpion Therapeutics/Pierre Fabre), STX-721/PFL-271 (Antares Therapeutics), A2B395 (A2 Biotherapeutics), BNT326 (YL 202) (BioNTech), DF9001 (Dragonfly Therapeutics), Pamvatamig (MCLA-129) (Merus), TAS3351 (Taiho Oncology), DB-1310 (DualityBio), Enozertinib (ORIC-114) (ORIC Pharmaceuticals), BG-60366 (BeOne Medicines), and others. Akeso's ivonescimab (AK112, SMT112) is a novel PD-1/VEGF bispecific antibody and the first agent of its kind to advance into Phase III clinical testing. Developed using the company's proprietary Tetrabody platform, the therapy is designed to simultaneously inhibit PD-1 interactions with PD-L1 and PD-L2 while also blocking VEGF from binding to its receptors. Simultaneous inhibition of the PD-1 and VEGF pathways has demonstrated notable clinical benefits across several cancers, including NSCLC, renal cell carcinoma, and hepatocellular carcinoma. By integrating both mechanisms into a single therapeutic molecule, ivonescimab may enable broader pathway suppression and potentially provide superior antitumor efficacy compared with conventional combination approaches. The US FDA has accepted Summit Therapeutics' Biologics License Application (BLA) for ivonescimab, supported by findings from the Phase III HARMONi trial, and has set a PDUFA action date of November 14, 2026. ArriVent BioPharma and Shanghai Allist Pharmaceuticals' Firmonertinib, previously referred to as furmonertinib, is an orally administered, mutation-selective EGFR inhibitor recognized for its strong CNS penetration and activity against a broad spectrum of EGFR mutations, including uncommon variants such as PACC and Exon 20 insertion mutations. The therapy is currently being investigated in the global Phase III FURVENT trial (NCT05607550) as a first-line option for NSCLC patients with EGFR Exon 20 insertion mutations. At the same time, the global Phase Ib FURTHER study (NCT05364043) is evaluating its efficacy in patients with EGFR PACC mutations. In addition, firmonertinib is being explored in combination regimens for advanced or metastatic NSCLC with classical EGFR mutations through a collaboration with InnoCare Pharma. Cullinan Therapeutics and Taiho Pharma's Zipalertinib is a next-generation, irreversible oral EGFR inhibitor specifically developed to selectively target tumors carrying EGFR exon 20 insertion mutations while sparing wild-type EGFR activity. Preclinical findings indicate that this mutant-selective design may help mitigate the toxicities commonly associated with inhibition of wild-type EGFR. The molecule's distinct chemical structure is also intended to minimize HER2 inhibition, thereby improving selectivity further. Due to its targeted mechanism and encouraging clinical data, zipalertinib is gaining attention as a potential treatment option for EGFR exon 20 insertion-mutated NSCLC. Taiho Pharmaceutical and Cullinan Therapeutics recently announced that the FDA has accepted the NDA for zipalertinib for patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations whose disease progressed after platinum-based chemotherapy, with or without prior amivantamab treatment. The application has been assigned a PDUFA target date of February 27, 2027. The anticipated launch of these emerging therapies are poised to transform the EGFR inhibitors market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the EGFR inhibitors market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. To know more about companies developing EGFR inhibitors, visit @ EGFR Inhibitors Treatment Recent Developments in the EGFR Inhibitors Market In April 2026, Taiho Oncology, Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. announced that the FDA had accepted the NDA for zipalertinib to treat patients with locally advanced or mNSCLC harboring EGFR ex20ins mutations whose disease has progressed following platinum-based chemotherapy, with or without prior amivantamab treatment. The FDA has assigned a PDUFA target action date of February 27, 2027. In February 2026, J INTS BIO announced that research findings on JIN-A02 had been published in Clinical Cancer Research, a leading oncology journal published by the American Association for Cancer Research (AACR). In February 2026, the FDA approved once-monthly RYBREVANT FASPRO + LAZCLUZE for 1L EGFR-mutated advanced NSCLC. In January 2026, the US FDA accepted for filing Summit's Biologics License Application (BLA) seeking approval for the HARMONi trial (Phase III). The FDA provided a Prescription Drug User Fee Act (PDUFA) goal action date of November 14, 2026. In December 2025, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for AUMSEQA in adult NSCLC, covering first-line EGFR-mutant disease and EGFR T790 M-mediated acquired resistance. What are EGFR Inhibitors? EGFR inhibitors are a class of targeted therapies designed to block the activity of the epidermal growth factor receptor (EGFR), a protein that plays a critical role in regulating cell growth, survival, and proliferation. In many cancers, including non-small cell lung cancer (NSCLC), colorectal cancer, head and neck cancer, and glioblastoma, EGFR is either overexpressed or mutated, leading to uncontrolled tumor growth. EGFR inhibitors work by interfering with the signaling pathways activated by this receptor, thereby slowing or stopping cancer cell proliferation. These therapies are broadly categorized into tyrosine kinase inhibitors (TKIs), which target the intracellular kinase domain of EGFR, and monoclonal antibodies, which bind to the extracellular portion of the receptor. Over the past decade, EGFR inhibitors have transformed the treatment landscape of several solid tumors by enabling more personalized and biomarker-driven therapeutic approaches. EGFR Inhibitors Epidemiology Segmentation The EGFR inhibitors market report is a comprehensive and specialized analysis, offering in-depth epidemiological insights for the study period 2022–2036 across the leading markets. The EGFR inhibitors target patient pool is segmented into: Total Incident Cases of EGFR Inhibitor Total Incident cases of EGFR by Indication Scope of the EGFR Inhibitors Market Report EGFR Inhibitors Patient Population Forecast EGFR Inhibitors Therapeutics Market Size EGFR Inhibitors Pipeline Analysis EGFR Inhibitors Market Size and Trends EGFR Inhibitors Market Opportunity EGFR Inhibitors Market Unmet Needs KOL's Views on EGFR Inhibitors EGFR Inhibitors Market Access and Reimbursement Discover the best emerging EGFR inhibitors in pipeline @ EGFR Inhibitors Clinical Trials Table of Contents Related Reports EGFR NSCLC Market EGFR NSCLC Market Insights, Epidemiology, and Market Forecast – 2036 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key EGFR NSCLC companies, including AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hansoh Pharmaceutical, Johnson & Johnson Innovative Medicine, Pfizer, Cullinan Oncology, Taiho Pharmaceutical, ArriVent Biopharma, Black Diamond Therapeutics, Daiichi Sankyo, Akeso Biopharma, Summit Therapeutics, and others. Non-Small Cell Lung Cancer Market Non-Small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2036 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies including BeiGene , Merus and Partner Therapeutics, Johnson & Johnson Innovative Medicine, Betta Pharma, Xcovery, CStone Pharmaceuticals, Bristol-Myers Squibb, Haihe Biopharma, Taiho Pharmaceutical, Takeda Pharmaceuticals, EMD Serono (Merck KGaA), Eli Lilly and Company, Merck, Regeneron, Sanofi, Ono Pharmaceutical, Novartis, Genentech, Roche, Amgen, Chugai Laboratories, Moderna Therapeutics, Pfizer, GSK and others. Colorectal Cancer Market Colorectal Cancer Market Insights, Epidemiology, and Market Forecast – 2036 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key CRC companies, including Shanghai Henlius Biotech, Agenus, Tizona Therapeutics, Surgimab, Novartis, Bexion Pharmaceuticals, Syndax Pharmaceuticals, Exelixis, AbbVie, Tyligand Pharmaceuticals, Bristol Myers Squibb, Eisai, Bold Therapeutics, Takeda, Merck Sharp & Dohme, and others Head and Neck Cancer Market Head and Neck Cancer Market Insights, Epidemiology, and Market Forecast – 2036 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key HNC companies, including CEL-SCI, Junshi Biosciences, Coherus, Exelixis, Immutep S.A.S., Merck Sharp & Dohme LLC, Iovance Biotherapeutics, BeiGene, Akeso, Chia Tai-Tianqing, Kura Oncology, Hoffmann-La Roche, Eli Lilly and Company, and others. 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导语：耐药困境与破局之路     以奥希替尼为代表的第三代EGFR-TKI已成为EGFR敏感突变晚期非小细胞肺癌（NSCLC）一线治疗的基石，显著改善了患者的无进展生存期（PFS）和总生存期（OS）。然而，约70%的患者在治疗12~24个月后会出现获得性耐药，导致疾病进展，这成为当前临床实践中的核心挑战。耐药机制复杂多样，主要包括EGFR依赖性突变（如C797S）、旁路信号激活（如MET扩增）和表型转化。肖东京等学者在《临床医学进展》发表的综述，系统梳理了耐药后的药物治疗策略演进，为临床决策提供了重要参考。本文将基于该综述，进行深度解读。               一、靶向治疗策略的精准调整：基于机制的“再定向”                                 1.1 针对C797S突变的“复古”与创新联合          C797S突变是三代TKI常见的耐药机制，其亚型（顺式、反式、单突变）对治疗选择有决定性影响。对于T790M/C797S顺式突变患者，一项回顾性研究显示，布加替尼联合西妥昔单抗方案的ORR达60%，中位PFS长达14个月，显著优于化疗。对于反式突变，奥希替尼联合一代TKI（如厄洛替尼）可短暂有效，但后续可能因突变构型转变而失效。而C797S单突变患者则可能从换用一/二代TKI中获益。这些探索性策略为等待第四代TKI等新药提供了重要的“过渡桥接”方案。                                                           1.2 双靶点联合：攻克旁路激活耐药                                当耐药源于MET扩增等旁路激活时，三代TKI联合MET抑制剂成为关键策略。两项里程碑式研究——SAVANNAH和INSIGHT 2——为此提供了高级别证据。                                SAVANNAH研究（II期）表明，奥希替尼联合赛沃替尼用于MET高度扩增/过表达患者，ORR可达49%，中位PFS延长至9.3个月（HR 0.44）。INSIGHT 2研究则评估了奥希替尼联合特泊替尼，在MET扩增患者中ORR为50%，中位PFS为5.6个月。这两项研究共同确立了MET异常作为联合治疗的生物标志物，并凸显了通过活检（IHC/FISH）进行精准筛选的重要性。                                此外，针对BRAF V600E等罕见耐药突变，奥希替尼联合BRAF/MEK抑制剂（达拉非尼+曲美替尼）的三联方案也显示出高达58.3%的ORR，中位PFS达13.5个月。这些数据强调了“再活检”明确耐药机制对于指导后续精准治疗的核心价值。               二、以化疗为基础的联合治疗：耐药后的“基石”策略                                当耐药机制不明确或尚无匹配的靶向药物时，以含铂双药化疗为基础的联合方案是当前指南推荐的主要选择。其核心思路是通过不同作用机制的药物组合，克服耐药性并延缓进展。                                 2.1 化疗联合靶向治疗                               一项多中心回顾性研究（Tejas等人）发现，在奥希替尼进展后，继续使用奥希替尼并联合培美曲塞+卡铂，相比单独化疗，可显著延长PFS（9.0个月 vs. 4.5个月，HR 0.49，p=0.0032），并能延缓中枢神经系统进展。这提示，即使疾病进展，原靶向药物在部分患者中仍可能通过抑制敏感克隆或协同作用贡献疗效。                                 2.2 化疗联合免疫检查点抑制剂（ICIs）                               回顾性数据表明，化疗联合ICIs治疗（如PD-1/PD-L1抑制剂）相较于单用ICIs，能显著改善奥希替尼耐药患者的生存（mPFS：5.7个月 vs. 1.5个月；mOS：18.2个月 vs. 4.9个月）。值得关注的是，既往对奥希替尼治疗反应持续时间较长（PFS > 10个月）的患者，从联合治疗中获益可能更显著。然而，这些结论主要基于小样本回顾性研究，亟需前瞻性临床试验验证。                                 2.3 化疗联合抗血管生成治疗                                ORIENT-31 III期研究为此提供了Ⅰ类证据。该研究评估了信迪利单抗（PD-1抑制剂）联合贝伐珠单抗生物类似物（IBI305）及化疗用于EGFR-TKI耐药后患者。结果显示，四药联合方案（免疫+抗血管+化疗）的中位PFS达到7.2个月，相比单独化疗（4.3个月）将疾病进展风险降低了49%（HR=0.51, p0.0001）。亚组分析显示，脑转移患者获益更为明显。该方案是目前循证等级较高的联合策略之一。                                                  以化疗为基础的联合方案疗效确切，但需高度关注其安全性。ORIENT-31研究中，四药联合组3级及以上不良反应发生率高达56%。因此，在选择此类方案时，必须充分评估患者的体能状态、合并症及耐受性，实现疗效与安全性的平衡。                            三、新药研发前沿：瞄准耐药，开辟新路  3.1 抗体药物偶联物（ADC）：精准的“生物导弹”                                ADC药物通过抗体精准递送细胞毒药物，在耐药后治疗中展现出潜力。                              • Dato-DXd（靶向TROP2）： 在TROPION-Lung01/05研究的汇总分析中，用于经奥希替尼治疗后的患者，ORR达44.8%，中位PFS为5.7个月。                  • HER3-DXd（靶向HER3）： HERTHENA-Lung01研究显示，用于奥希替尼经治患者，ORR为29.2%，中位PFS为5.5个月。                  • AZD9592（靶向EGFR/c-MET）： 临床前研究显示良好活性，I期临床试验正在进行中。                          笔者认为，Dato-DXd的临床数据相对成熟，有望率先改变EGFR-TKI耐药后的治疗格局。                                 3.2 第四代EGFR-TKI：征途漫漫                                针对C797S突变开发的第四代TKI（如BDTX-1535）在早期研究中显示出初步活性（ORR可达55%）。然而，整体研发挑战巨大，目前尚无药物进入III期临床，部分代表性药物（如BLU-945）已停止开发。其研发之路仍需更多突破。                                 3.3 双特异性抗体：一箭双雕                                同时靶向两个关键通路的双特异性抗体是另一大热点。                               • 埃万妥单抗（靶向EGFR/MET）： III期MARIPOSA-2研究证实，与单纯化疗相比，含埃万妥单抗的方案可显著延长PFS（8.3个月 vs. 4.1个月），并降低50%以上的死亡风险。但需注意其较高的3级以上不良反应率。                  • 依沃西单抗（靶向PD-1/VEGF）： III期研究显示，其联合化疗用于EGFR-TKI耐药患者，中位PFS显著优于化疗（7.1个月 vs. 4.8个月）。                           这两种双抗均已在国内获批，为耐药后治疗提供了新的强效武器。                                                         四、总结与展望：耐药后的临床决策路径 第三代EGFR-TKI耐药后的治疗已进入一个多元化、精准化的新阶段。基于现有证据，可梳理出以下核心要点与临床路径：                                再活检是决策基石： 无论采用何种方案，尽可能获取组织或液体活检明确耐药机制，是实现精准治疗的前提。              靶向调整优先： 若明确特定耐药靶点（如MET扩增、C797S、BRAF等），优先考虑对应的靶向联合治疗方案（如奥希替尼+赛沃替尼/特泊替尼），以获取更优的疾病控制。             联合化疗是可靠“压舱石”： 在机制不明或无匹配靶向药时，以化疗为基础的联合策略（特别是免疫+抗血管+化疗的四药方案）提供了经高级别证据验证的有效选择。              新药带来新希望： ADC药物（如Dato-DXd）和双特异性抗体（如埃万妥单抗、依沃西单抗）在临床试验中表现突出，部分已获批，正在重塑治疗格局。              安全性管理不容忽视： 联合治疗，尤其是多药联合，常伴随更高的不良反应发生率。治疗方案的选择需充分权衡疗效与患者的耐受性，实施个体化管理。                                未来，随着对耐药机制理解的深入，以及更多新药（如第四代TKI、新型ADC）的研发和临床研究数据的积累，三代EGFR-TKI耐药后的治疗将更加精准和有效。临床医生需要持续关注进展，为每一位耐药患者量身定制最优的序贯治疗方案。               参考文献   [1] Cheng Y, et al. 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Lung Adenocarcinoma Harboring EGFR T790M and in Trans C797S Responds to Combination Therapy of First- and Third-Generation EGFR TKIs. J Thorac Oncol, 2017.