MK-1084

With increasing biomarker-driven cancer treatments, TEPMETKO benefits from growing adoption in precision oncology. Competition from other MET inhibitors like TABRECTA (capmatinib) exists, but TEPMETKO's once-daily dosing and efficacy profile offer differentiation. LAS VEGAS, March 6, 2025 /PRNewswire/ -- DelveInsight's " TEPMETKO Market Size, Forecast, and Market Insight Report" highlights the details around TEPMETKO, a kinase inhibitor indicated for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of TEPMETKO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. EMD Serono's TEPMETKO (tepotinib) Overview TEPMETKO is a kinase inhibitor prescribed for adult patients with metastatic non-small cell lung cancer (NSCLC) carrying MET exon 14 skipping alterations. The active component is Tepotinib (as hydrochloride monohydrate), administered orally. Patients should be cautioned about the heightened risk of severe or fatal interstitial lung disease/pneumonitis, liver toxicity, and potential embryo-fetal toxicity, necessitating effective contraception during and shortly after treatment. Tepotinib specifically targets MET, including variants with exon 14 skipping mutations. It blocks HGF-dependent and independent MET phosphorylation, disrupting MET-driven signaling pathways. Additionally, at clinically relevant concentrations, Tepotinib inhibits melatonin 2 and imidazoline 1 receptors. In vitro studies show that it suppresses tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent cancer cells. In mouse models with MET-driven tumors, including those with MET exon 14 skipping alterations, Tepotinib reduced tumor growth, sustained MET phosphorylation inhibition, and, in one case, decreased metastasis formation. The recommended dose of TEPMETKO is 450 mg taken orally once daily until disease progression or intolerable toxicity occurs. Patients should take it at the same time each day, swallowing tablets whole without chewing, crushing, or splitting them. If a dose is missed and less than eight hours remain until the next scheduled dose, patients should skip it. In cases of vomiting after taking TEPMETKO, the next dose should be taken at the usual time. Learn more about TEPMETKO projected market size for NSCLC @ TEPMETKO Market Potential Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 81% of all diagnosed cases. Early detection greatly improves outcomes, but diagnosing NSCLC and other lung cancers is challenging because their symptoms are often mistaken for common illnesses or the long-term effects of smoking. Consequently, 80% of NSCLC cases are already at advanced stages by the time they are identified, making treatment more difficult. Around 80% of EGFR mutations in NSCLC involve either exon 19 deletions or the exon 21 L858R substitution, both of which are classified as sensitizing mutations. Until the last decade, chemotherapy was the primary treatment for advanced and metastatic lung cancer. However, this changed in 2015 with the approval of the first immune checkpoint inhibitor (ICI), KEYTRUDA (pembrolizumab), as a second-line therapy for advanced cases. This was followed by TECENTRIQ (atezolizumab) in 2016. Both therapies were later approved for first-line treatment, broadening their use to a larger patient population. In 2020, the combination of OPDIVO (nivolumab) and ipilimumab also received approval as a first-line treatment for metastatic NSCLC. According to DelveInsight, the NSCLC market size across the 7MM is projected to grow from USD 30 billion in 2024, with a substantial CAGR through 2034. This growth is largely driven by the introduction of emerging therapies during the forecast period (2025–2034). Discover more about the NSCLC market in detail @ Non-small Cell Lung Cancer Market Report Emerging Competitors of TEPMETKO The NSCLC pipeline is very robust with the promising therapies such as Telisotuzumab vedotin (AbbVie), Patritumab deruxtecan (Daiichi Sankyo/AstraZeneca), Datopotamab deruxtecan (Daiichi Sankyo/AstraZeneca), Eftilagimod alpha (Immutep), BNT311/GEN1046 (acasunlimab) (Genmab), V940 (mRNA-4157) + Pembrolizumab (Moderna Therapeutics/Merck), Plinabulin + Docetaxel (BeyondSpring), Olomorasib (LY3537982) (Eli Lilly and Company), Zipalertinib (Cullinan Oncology/Taiho Pharma), Ceralasertib (AZD6738) (AstraZeneca), TEDOPI (EP-2101; IDM 2101; OSE-2101) (OSE Immuno-therapeutics), Sigvotatug vedotin (PF08046047) (Pfizer), ANKTIVA (N-803) (ImmunityBio), Aumolertinib/Almonertinib/HS-10206 (Jiangsu Hansoh Pharmaceutical), Niraparib (GSK), Savolitinib (AstraZeneca/Hutchison MediPharma), TRODELVY (Gilead Sciences), Pyrotinib (Jiangsu HengRui Medicine), Ociperlimab (BGB-A1217) (BieGene), Volrustomig (AstraZeneca), Gotistobart (BNT316/ONC-392) (OncoC4/BioNTech), Ivonescimab (AK112/SMT112) (Akeso Biopharma/Summit Therapeutics), ZYNYZ (retifanlimab/INCMGA00012) (Incyte/Macrogenics), Divarasib (GDC-6036) (Roche/Genentech), Tiragolumab (RG6058) (Roche), Sacituzumab Tirumotecan (Merck and Kelun-Biotech), JEMPERLI (dostarlimab/TSR-042) (GSK and AnaptysBio), Zongertinib (BI-1810631) (Boehringer Ingelheim), BAY 2927088 (Bayer), Serplulimab (HLX10) (Shanghai Henlius Biotech), Rilvegostomig (AZD2936) (AstraZeneca), MK-1084 (Merck, Taiho Pharmaceutical, and Astex), Domvanalimab (Arcus Biosciences and Gilead Sciences), OPDUALAG (nivolumab and relatlimab) (Bristol-Myers Squibb), Belrestotug + JEMPERLI (iTeos Therapeutics and GSK), Firmonertinib (ArriVent BioPharma), Sunvozertinib (DZD9008) (Dizal Pharmaceutical), Cobolimab (GSK), Livmoniplimab (AbbVie), Fianlimab (REGN3767) (Regeneron Pharmaceuticals), BNT327/PM8002 (Biotheus/BioNTech), HS-20117 (Hansoh BioMedical), IO102-IO103 + Pembrolizumab (IO Biotech), Naptumomab estafenatox (NeoTX Therapeutics/Active Biotech), FF-10832 (FUJIFILM Corporation), BNT116 (BioNTechSE/Regeneron Pharmaceuticals), CAN-2409 (Candel Therapeutics), Mecbotamab Vedotin (BA3011/CAB-AXL-ADC) (BioAtla), Bemcentinib (BGB 324/BGB-3234/R-428) (BerGenBio/Rigel Pharmaceuticals), DOVBLERON (taletrectinib/AB-106/IBI-344) (Nuvation Bio/Innovent Biologics/Daiichi Sankyo/Nippon Kayaku), Lifileucel (Iovance Biotherapeutics), IBI363 (Innovent Biologics), Sotevtamab (AB-16B5) (Alethia Biotherapeutics), Avutometinib (VS6766) (Verastem Oncology), Vebreltinib (APL-101) (Apollomics), LP-300 (Lantern Pharma), JNJ-90301900 (Johnson & Johnson Innovative Medicine), AMG 193 (Amgen), Luveltamab tazevibulin (Sutro Biopharma), PRT3789 (Prelude Therapeutics), Disitamab vedotin (Seagen), PADCEV (enfortumab vedotin) (Astellas Pharma), RP1 (Replimune), TIVDAK (tisotumab vedotin) (Seagen), Zanidatamab (Jazz Pharmaceuticals), Utidelone injectable (UTD1) (Beijing Biostar Pharmaceuticals), REGN5093-M114 (Regeneron Pharmaceuticals), SLC-391 (SignalChem Lifesciences), fulzerasib (GenFleet), Davutamig (REGN5093) (Regeneron Pharmaceuticals), TAS3351 (Taiho Oncology), H002 (RedCloud Bio), JIN-A02 (J INTS BIO), FWD1509 (Forward Pharma), Sabestomig (AZD7789) (AstraZeneca), Sasanlimab (Pfizer), Selvigaltin (GB1211) (Galecto Biotech), Vepafestinib Helsinn (Healthcare/Taiho Pharmaceutical), EP0031 (A400/ KL590586) (Ellipses Pharma/Kelun-Biotech), Pamvatamig (MCLA-129) (Merus), Zidesamtinib (NVL-520) (Nuvalent), NVL-655 (Nuvalent), RMC-4630 (Revolution Medicines), REQORSA (quaratusugene ozeplasmid) (Genprex), PDC*lung01 (PDC*line Pharma), Evalstotug (BA3071) (BioAtla and BeiGene), PT-112 (Promontory Therapeutics), MRT-2359 (Monte Rosa Therapeutics), GAIA-102 (GAIA BioMedicine), Rigosertib (Traws Pharma), HMBD-001 (Hummingbird Bioscience), PLB1004 (Avistone Biotechnology), ANS03 (Avistone Biotechnology), MYTX-011 (Mythic Therapeutics), A166 (Sichuan Kelun-Biotech Bio-pharmaceutical), Atamparib (BN-2397) (Ribon Therapeutics), DELTACEL (KB-GDT-01) (Kiromic BioPharma), Carotuximab (ENV-105) (Kairos Pharma), YL202 (MediLink Therapeutics), and others. To know more about the number of competing drugs in development, visit @ TEPMETKO Market Positioning Compared to Other Drugs Key Milestones of TEPMETKO In February 2024, the FDA granted traditional approval to TEPMETKO for adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. In February 2022, the EC approved TEPMETKO as monotherapy for the treatment of adult patients with advanced NSCLC harboring alterations leading to METex14 skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy. In February 2021, Merck announced that the US FDA has approved TEPMETKO following priority review for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. This indication was approved under accelerated approval based on ORR and DOR. In October 2020, TEPMETKO received ODD for treating NSCLC with MET genomic tumor aberrations In March 2020, EMD Serono (the biopharmaceutical business of Merck KGaA), announced that the MHLW approved TEPMETKO for the treatment of patients with unresectable, advanced, or recurrent NSCLC with METex14 skipping alterations. In September 2019, the US FDA granted BTD for tepotinib in patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy Discover how TEPMETKO is shaping the NSCLC treatment landscape @ TEPMETKO NSCLC TEPMETKO Market Dynamics TEPMETKO competes in a growing but highly specialized market where MET-targeted therapies are gaining traction due to their efficacy in addressing MET-altered tumors. The market for MET inhibitors is expanding as precision oncology advances and molecular diagnostics become more widely available, enabling better identification of patients who would benefit from targeted treatments like TEPMETKO. A key factor shaping TEPMETKO's market dynamics is competition. It directly competes with Novartis' TABRECTA (capmatinib), another MET inhibitor approved for the same indication. While TEPMETKO offers the advantage of once-daily dosing compared to TABRECTA's twice-daily regimen, both drugs have similar efficacy profiles, making physician and patient preference an important differentiator. Additionally, broader competition from next-generation MET inhibitors and combination therapies in clinical trials could impact TEPMETKO's long-term market position. Regulatory approvals and market access play a crucial role in TEPMETKO's adoption. The drug has been approved in multiple regions, including the U.S., Europe, and Japan, but reimbursement and pricing strategies vary by market. Payer policies, along with the cost-benefit analysis of MET inhibitors compared to other targeted therapies, influence prescription trends. Furthermore, real-world evidence and post-marketing studies will be critical in demonstrating TEPMETKO's sustained effectiveness and safety, which could support expanded indications and increased market penetration. Looking ahead, the MET inhibitor market is expected to grow with advances in biomarker-driven therapy, further refining patient selection. TEPMETKO's success will depend on continued clinical development, potential label expansions, and strategic partnerships to strengthen its competitive edge. As new entrants emerge, Merck KGaA's ability to differentiate TEPMETKO through combination strategies or enhanced formulations may determine its long-term sustainability in this evolving landscape. Dive deeper to get more insight into TEPMETKO's strengths & weaknesses relative to competitors @ TEPMETKO Market Drug Report Table of Contents Related Reports Non-small Cell Lung Cancer Market Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver 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 Daiichi Sankyo, AstraZeneca, Gilead Sciences, BieGene, AbbVie, Roche, Merck, Novartis, Pfizer, Takeda Pharmaceuticals, Eli Lilly, BerGenBio, GlaxoSmithKline, Duality biologics, among others. Non-small Cell Lung Cancer Pipeline Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key non-small cell lung cancer companies, including BridgeBio Pharma, Daiichi Sankyo, EMD Serono, Merck, BridgeBio Pharma, Abbvie, Pfizer, Eli Lilly and Company BioNTech SE, Shenzhen TargetRx, Taiho Pharmaceutical, Chong Kun Dang, Bristol Myers Squibb, Innovent Biologics, Xuanzhu Biopharmaceutical, Bayer, GeneScience Pharmaceuticals, InventisBio, Apollomics, Imugene, Ono Pharmaceutical, Pierre Fabre, Jiangsu Hengrui Medicine Co., Bristol-Myers Squibb, Surface Oncology, Inhibrx, Sinocelltech, Mirati Therapeutics, REVOLUTION Medicines, Yong Shun Technology Development, Iovance Biotherapeutics, Galecto Biotech, among others. C-MET Metastatic Non-small Cell Lung Cancer Market C-MET Metastatic Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key C-MET mNSCLC companies, including Novartis, Merck, EMD Serono, AbbVie, Regeneron Pharmaceuticals, Mythic Therapeutics, Apollomics, Johnson & Johnson Innovation, Haihe Biopharma, among others. C-MET Non-small Cell Lung Cancer Pipeline C-MET Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key C-MET non-small cell lung cancer companies, including AbbVie, Janssen Research & Development, Beijing Pearl Biotechnology Limited Liability Company, Novartis, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

关注并星标CPHI制药在线 近日，KRAS赛道热闹非凡，作为早期最著名的不可成药靶点之一，近几年随着Sotorasib以及Adagrasib的获批上市，不仅打破了KRAS不可成药的魔咒，同时也迅速激发了这一赛道的研发热情。 最近几天，KRAS又迎来了重大突破，7月15日Revolution Medicines公布泛KRAS抑制剂RMC-6236的1b期临床积极结果：RMC-6236单药二线治疗KRAS G12X突变PDAC（胰腺导管腺癌）患者，可使患者的中位无进展生存期（PFS）达8.1个月，疾病控制率（DCR）达近90%。据悉，Revolution Medicines已经在准备开展PDAC患者二线疗法的临床Ⅲ期试验，以比较每日一次的RMC-6236对比化疗在二线PDAC患者治疗的差异性。众所周知，胰腺癌是最难以解决的肿瘤类型，而随着RMC-6236的积极进展，KRAS抑制剂的价值又得到了进一步印证。 与此同时，不仅在抗肿瘤适应症上全面开花，KRAS抑制剂在其他适应症上也有所斩获。近期《新英格兰医学杂志》（NEJM）发布的一项研究发现，除了癌症，KRAS靶向疗法还可成功被用以治疗一种称之为动静脉畸形（AVM）的疾病。接受治疗患者的症状显著缓解，其中一位患者不再需要住在重症监护室（ICU），另一位患者则在治疗后恢复受损的听力。KRAS抑制剂对不同疾病的巨大治疗潜力以及未充分竞争的蓝海市场，吸引了包括罗氏、诺华、BMS等多个巨头在内的竞争，在全球范围内迅速开启KRAS抑制剂军备竞赛。 01 01 巨头之争 Sotorasib和Adagrasib是目前仅有的两款已上市KRAS G12C抑制剂，分别于2021年5月和2022年12月上市，其中前者来自安进，后者来自Mirati Therapeutics（已被BMS收购），Sotorasib获批用于二线治疗KRAS G12C突变的非小细胞肺癌，Adagrasib（MRTX849）也在同一适应症获批上市，并将KRAS抑制剂的应用扩展与西妥昔单抗联合用于KRAS G12C突变的结直肠癌。 但这两款药物在上市后均遭遇了不同挫折，Sotorasib上市后的表现却不尽如人意，2021年、2022年以及2023年销售额分别仅有0.9亿美元、2.85亿美元、2.80亿美元，远低于市场预期且甚至在需要放量的时候遭遇了销售额下滑。祸不单行，2023年10月，FDA ODAC认为Sotorasib Ⅲ期试验主要研究终点盲态独立中心评估的无进展生存期（PFS）无法被可靠地解释，不能支持其疗效优势，意味着可能面临撤回加速批准或退市风险。Adagrasib也并非一帆风顺，在被欧盟拒绝附条件批准后跌跌撞撞半年后重新撞线，商业化表现自然也是一言难尽，去年前三季度仅仅拿下0.36亿美元的销售额，在被BMS全面接手商业化后，本年度第一季度也仅仅拿下2100万美元的销售额，也大大不如预期。 背后原因不难理解，Sotorasib与Adagrasib的临床研究数据都不够理想：ORR均在40%左右，PFS中位数改善约5个月，且均显示一定肝毒性。不过Sotorasib和Adagrasib都将重头戏放在了一线治疗KRAS G12C突变的非小细胞肺癌之上，但并没有将先发优势转化为商业化优势的两款药物，也将要面临后面仅仅追赶的多款药物的竞争，竞争者们就包括了罗氏、默沙东、诺华等多家巨头。 罗氏已率先发难，近日clinicaltrials网站显示，罗氏启动了KRAS G12C抑制剂Divarasib（每日1次）对比Sotorasib（每日1次）或Adagrasib（每日2次）治疗经治KRASC G12C阳性的晚期或转移性非小细胞肺癌（NSCLC）患者的头对头III期研究。该研究是第一项直接比较不同KRAS G12C抑制剂疗效的III期临床试验。罗氏的策略也很明确，等Sotorasib或Adagrasib获得完全批准并成为标准疗法之后，再开始进行头对头试验，进可攻退可守。而礼来以及默沙东的策略稍微激进一些，和罗氏先从二线治疗非小细胞肺癌出发不同的是，默沙东以及礼来各自的候选药物MK-1084和Olomorasib甚至直接选择冲击一线疗法，不过最早也需要等到2026年底预计读取临床数据，在时间上并不具备优势。 2024年ASCO，礼来报告了其第二代KRAS抑制剂 Olomorasib（LY3537982）的1/2期研究LOXO-RAS-20001 中联合K药在NSCLC上的结果，其中Olomorasib的剂量为50mg BID或100mg BID。疗效上展现出积极信号。经治NSCLC的ORR 40%，DCR 81%; 一线NSCLC的ORR达到77%，DCR 88%。 图1：目前KRAS抑制剂在非小细胞肺癌临床布局情况 但令人遗憾的是，巨头中也已经有人悄悄掉队。就在近两个月，诺华放弃了其临床Ⅲ期的KRAS G12C抑制剂Opnurasib（JDQ443），从已公布的临床数据看来，Opnurasib展现的不错疗效数据。2023年美国临床肿瘤学会（ASCO）年会上，诺华公布了Opnurasib单药治疗 KRAS G12C突变实体瘤的 Ib/II期研究数据。对于20名NSCLC患者，在所有剂量水平组的客观缓解率（ORR）为45.0%，接受推荐剂量200mg BID的NSCLC患者的ORR可达57.1%，疾病控制率（DCR）达92.9%。诺华放弃的原因目前尚未得知，不过可以猜测的是，大概率是诺华对于目前其肿瘤管线的战略调整，未来存在重新启动的可能性。 02 02 第二战场 以Sotorasib为代表的第一代KRAS抑制剂首先在GTP酶口袋中形成较为松散的药物-蛋白相互作用，随后迅速形成不可逆的共价结合。首个获批的KRAS抑制剂sotorasib成功证明了抑制KRAS是可实现的，但是这种抑制剂仅对携带G12C突变的KRAS蛋白（约占20%）有效，而更多携带G12D和G12V突变的肿瘤患者不能从该药物中受益，故G12D和G12V突变的肿瘤目前存在巨大尚未满足的临床需求。 图2：HRS-4642 I 期临床试验相关数据 （数据来源：2023 ESMO） 目前除了Mirati Therapeutics 研发的MRTX1133针对KRAS G12D之外，由恒瑞医药开发的HRS-4642是一种高度选择性的KRAS G12D抑制剂。在NCT05533463的I期研究中，18名携带KRAS G12D突变的晚期实体瘤患者（包括10名NSCLC患者）接受了治疗。初步结果显示，11名患者（61%）病情稳定，6名患者（33%）的靶病变缩小。 随着上文中提到的Revolution Medicines开发的泛KRAS抑制剂RMC-6236在胰腺癌上取得的重大突破，将更多人的目光，也锁定在了泛KRAS（pan-KRAS）抑制剂上，RMC-6236可以将亲环蛋白A结合到所有形式的KRAS和相关的NRAS和H-RAS癌蛋白上。泛KRAS抑制剂优点明显，首先是更广泛的覆盖患者群体，其次还能被用于解决耐药性问题，如首先在KARS突变体中使用突变体选择性抑制剂，产生耐药性后再选用泛KRAS抑制剂，从而在后期获得额外的临床效益。不过目前除了RMC-6236之外，其他泛RAS抑制剂目前进度较慢，仍需等待临床验证。 与此同时，分子胶药物、组合策略与RTK-MAPK通路抑制、免疫疗法及自噬抑制在治疗KRAS突变肿瘤方面显示出显著前景。分子胶药物通过将特定分子粘附在目标蛋白上，抑制其功能，目前有包括三复合抑制剂以及靶向蛋白降解剂分子胶药物正处于早期临床开发阶段。而作为如今癌症治疗的黄金疗法，KRAS抑制剂同免疫疗法的联合治疗同样也在全速推进状态，索Sotorasib与K药或阿替利珠单抗联合使用显示出协同效应。 除了同免疫疗法的联合治疗之外，KRAS抑制剂同TCR-T细胞疗法以及mRNA疫苗的联用目前也还在临床前期，mRNA-5671 由Moderna开发，是一款针对 KRAS G12C，G12D，G12V 和 G13D 等多种突变体的癌症疫苗。mRNA-5671 能够在体内制造抗原，以启动 T 细胞寻找和破坏表达四种关键 KRAS 突变体（G12C、G12D、G12V 和 G13C）的细胞。在一项 I 期试验中，Moderna 和默沙东正在携带 KRAS 突变或转移性的非小细胞肺癌、结直肠癌或胰腺癌患者中测试 mRNA-5671 单药治疗和 mRNA-5671+K药联合治疗的潜力。 03 03 国产谁将首先冲线 尽管Sotorasib以及Adagrasib已经在全球一些国家上市，但目前这两款药物仍未在国内获批，这就意味着，国内首款获批的KRAS抑制剂鹿死谁手还不一定，国产KRAS抑制剂仍有弯道超车的机会。 目前，劲方医药的Fulzerasib为首款申报上市的国产KRAS G12C抑制剂。去年11月，信达生物/劲方医药递交了KRAS G12C抑制剂Fulzerasib单药的上市申请，作为晚期NSCLC患者的二线单药治疗方案。另外，益方生物/正大天晴的Garsorasib、加科思的Glecirasib分别于2023年12月和2024年5月提交了上市申请，但上述三款药物也均是针对KRAS G12C突变，同Sotorasib和Adagrasib保持一致。 不过目前国内KRAS G12C的布局已经略显拥挤，一些企业开始将目光投向KRAS基因的其他突变位点，目前KRAS G12D、KRAS G13V、泛KRAS等的新药研发也在有序推进，除了上文中已经提及的恒瑞开发的KRAS G12D突变的靶向药物HRS-4642，目前加科思所研发的一款口服泛KRAS抑制剂JAB-23400，其目前在在体内和体外均具有较好的抗癌效果。JAB-23400能够同时抑制KRAS 激活与非激活状态，同时对HRAS、NRAS无抑制作用。 劲方医药也在今年的AACR会议上公布了口服泛RAS（ON）抑制剂GFH547临床前研究数据。GFH547为机制独特的口服小分子泛RAS（ON）抑制剂，采用三复合物作用机制（GFH547-CypA-RAS），可抑制多数肿瘤中常见的KRAS突变型（G12C、G12D、G12V等）以及NRAS、HRAS亚型蛋白。 总而言之，KRAS抑制剂目前还仍是一片蓝海市场，而谁能杀出重围，必须要看入局者的推进速度，从打破不可成药的魔咒，从0到1，KRAS花了40年的时间，这里面并没有中国企业去参与，而从1到10，绝对少不了中国创新力量的身影。 参考资料：        1、Sotorasib for Vascular Malformations Associated with KRAS G12C Mutation. N Engl J Med. 2024 Jul 17. doi: 10.1056/NEJMoa2309160. Epub ahead of print. PMID: 39018528. 2、Roche declares KRAS war on Amgen and Bristol，from oncologypipeline； 3、Novartis drops out of KRAS，from oncologypipeline； 4、The next generation of KRAS targeting: reasons for excitement and concern，Mol Cancer Ther，doi:10.1158/1535-7163.MCT-22-0356 5、Asher Mullard. The KRAS crowd targets its next cancer mutations. Nature Reviews Drug Discovery. 2023. 6、The next-generation KRAS inhibitors…What comes after sotorasib and adagrasib? DOI:10.1016/j.lungcan.2024.107886 END 【智药研习社抗体系列直播预告】 来源：CPHI制药在线 声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。 投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~