Lazertinib Mesylate

Median overall survival, a secondary endpoint, reached nearly 3.5 years with Johnson & Johnson's RYBREVANT® plus LAZCLUZE® in atypical EGFR-mutated disease Consistent responses observed across atypical EGFR mutation subgroups, including those historically associated with poorer outcomes ASCO 2026 results reinforce the significance of RYBREVANT®-based regimens for patients across EGFR mutations May 29, 2026 -- Johnson & Johnson (NYSE:JNJ) today announced updated results from the Phase 1/1b CHRYSALIS-2 study evaluating intravenous RYBREVANT® (amivantamab-vmjw) in combination with LAZCLUZE® (lazertinib) in patients with advanced non-small cell lung cancer (NSCLC) with atypical epidermal growth factor receptor (EGFR) mutations. The analysis showed encouraging long-term outcomes with RYBREVANT® plus LAZCLUZE® in this difficult-to-treat population. Median overall survival, a secondary endpoint, was nearly 3.5 years.1 The primary endpoint of objective response rate was previously reported.2 These results add to the growing body of evidence demonstrating the potential of RYBREVANT® plus LAZCLUZE® to deliver durable survival outcomes across both common and atypical EGFR-mutated advanced NSCLC in the first-line setting. Data were presented in an oral session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #8501).1 Patients with atypical EGFR-mutated NSCLC tend to have poorer outcomes than those with common EGFR mutations (exon 19 deletions and L858R substitutions), and effective first-line treatment options remain limited.3,4 These mutations represent approximately 10-20 percent of all EGFR-mutated cases.5 Median overall survival with current standard of care single-agent therapies remains under two years, highlighting a significant unmet need for treatments that can deliver more durable benefit in this setting.6,7 RYBREVANT® is designed to dual target EGFR and mesenchymal-epithelial transition (MET), while engaging the immune system.8,9,10,11 These complementary mechanisms play a central role in tumor growth and treatment resistance and may help address the underlying drivers of disease. "For patients with non-small cell lung cancer harboring atypical EGFR-mutations, first-line treatment decisions are often clouded by uncertainty regarding the efficacy of currently available EGFR tyrosine kinase inhibitors," said Joel Neal,* M.D., Ph.D., principal investigator of the Phase 1/1b CHRYSALIS-2 study. "The responses we've seen in this trial suggest the potential for more durable disease control, and the overall survival data reinforce that picture. These long-term outcomes begin to change how we think about treatment options in managing this subtype of lung cancer." Neal is also a Professor of Medicine in the Division of Oncology at Stanford Medicine. "Disease progression and molecular resistance remain critical barriers in EGFR-mutated non-small cell lung cancer," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. "RYBREVANT-based combinations demonstrate the power of changing the biology by addressing multiple disease drivers from the start rather than relying on single-pathway strategies. With strong outcomes across all known EGFR mutations, this approach is raising the bar for what first-line treatment can achieve." In Cohort C of the CHRYSALIS-2 study, RYBREVANT® plus LAZCLUZE® was evaluated as a first-line treatment in patients with atypical EGFR-mutated advanced NSCLC, excluding EGFR exon 20 insertion mutations (n=49). The most common atypical EGFR mutations included G719X (55 percent), S768X (27 percent) and L861X (24 percent), with 35 percent of patients harboring multiple atypical mutations. The study previously reported an objective response rate of 57 percent (primary endpoint).1,2 Median overall survival with RYBREVANT® plus LAZCLUZE® reached nearly 3.5 years (41.0 months; 95 percent confidence interval [CI], 27.7-not estimable) at a median follow-up of 31.3 months. Overall survival rates were 55 percent at three years and 46 percent at four years.1 Consistent clinical activity was observed across atypical EGFR mutation subgroups, as well as across patient and disease characteristics such as central nervous system metastases and TP53 status. Patients were also able to remain on treatment long-term across mutation groups and baseline characteristics. Notably, 41 percent of patients remained on RYBREVANT® for two years or longer, further supporting the durable survival observed with this combination.1 The safety profile of RYBREVANT® plus LAZCLUZE® was consistent with previous reports, with no new safety signals observed with longer follow-up. Most adverse events were Grade 1 or 2. The most common treatment-emergent adverse events occurring in more than 30 percent of patients included paronychia (78 percent), rash (65 percent), hypoalbuminemia (61 percent) and infusion-related reactions (61 percent).1 RYBREVANT®-based regimens are approved for patients with EGFR-mutated advanced NSCLC across common (exon 19 deletions and exon 21 L858R substitution mutations) and exon 20 insertion mutations, including in the first-line setting.12 These results further define long-term outcomes with first-line RYBREVANT® plus LAZCLUZE® for patients with atypical EGFR mutations. Additional data being presented at ASCO 2026 in lung, head and neck, and colorectal cancers underscore the broader potential of RYBREVANT® across tumor types. CHRYSALIS-2 (NCT04077463) is an open-label Phase 1/1b study to evaluate the safety and pharmacokinetics of LAZCLUZE®, a third-generation EGFR-TKI, as monotherapy or in combinations with RYBREVANT®, a human bispecific EGFR and cMet antibody in participants with advanced NSCLC. The study enrolled 460 patients with advanced NSCLC.13 Cohort C of the ongoing CHRYSALIS-2 study evaluates patients with atypical EGFR-mutated advanced NSCLC, excluding exon 20 insertion and classical EGFR mutations, who are treatment-naïve or have received up to two prior lines of therapy. Patients received intravenous RYBREVANT® in combination with LAZCLUZE® administered orally once daily.13 Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.14,15 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.16 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.17 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.14,15,18,19,20,21 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.22 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.23,24 EGFR exon 20 insertion mutations are the third-most prevalent activating EGFR mutation.25 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.26 RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) received U.S. FDA approval in December 2025 and is approved in multiple markets worldwide for the treatment of adults with EGFR-mutated non-small cell lung cancer (NSCLC), including those with exon 19 deletions, exon 21 L858R substitution mutations, and exon 20 insertion mutations. It is the only subcutaneous therapy approved in these populations and can be used as monotherapy or in combination with LAZCLUZE® (lazertinib) or chemotherapy in the front- and second-line settings, offering convenient monthly† or bi-weekly dosing. RYBREVANT FASPRO™ is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology. RYBREVANT® (amivantamab-vmjw), administered intravenously, received U.S. FDA approval in March 2024 and is approved for the same indications as RYBREVANT FASPRO™ across multiple markets. RYBERVANT® is a first-in-class, fully human bispecific antibody targeting EGFR and MET, designed to inhibit tumor growth while engaging the immune system. The effectiveness of RYBREVANT FASPRO™ is supported by the established clinical profile of RYBREVANT®, including data from multiple Phase 3 studies such as MARIPOSA, which demonstrated improvements in progression-free and overall survival when used in combination with LAZCLUZE® in first-line advanced EGFR-mutated NSCLC. The National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)‡ 27 include amivantamab-vmjw (RYBREVANT®) across its FDA-approved treatment settings, including as a Category 1 preferred option in combination with lazertinib (LAZCLUZE®) for first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. Subcutaneous amivantamab and hyaluronidase-lpuj (RYBREVANT FASPRO™) may be substituted for IV amivantamab-vmjw (RYBREVANT®) where appropriate. See the latest NCCN Guidelines® for NSCLC for complete information.§ || The NCCN Guidelines for Central Nervous System Cancers also include amivantamab (RYBREVANT®)-based regimens, including in combination with lazertinib (LAZCLUZE®), as the only NCCN-preferred combination options for patients with EGFR-mutated NSCLC and brain metastases. Beyond NSCLC, RYBREVANT-based therapies are being investigated across other solid tumors, including head and neck and colorectal cancers. In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of LAZCLUZE® (marketed as LECLAZA in South Korea). LAZCLUZE® is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. An analysis of the efficacy and safety of LAZCLUZE® from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023.28 The legal manufacturer for LAZCLUZE® is Janssen Biotech, Inc. and Yuhan Corporation.INDICATIONS At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity. Source: Johnson & Johnson 1 Neal JW, et al. Overall survival of first-line amivantamab plus lazertinib in atypical EGFR-mutated advanced NSCLC: Updated results from the CHRYSALIS-2 study. Presented at: 2026 ASCO Annual Meeting; 2026; Chicago, IL. 2 Tomasini P, Wang Y, Li Y, et al. Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non-Small Cell Lung Cancer: Results From CHRYSALIS-2. J Clin Oncol. 2026;44(1):54-65. doi:10.1200/JCO-24-02835 3 Kim EY, Cho EN, Park HS, et al. Compound EGFR mutation is frequently detected with co-mutations of actionable genes and associated with poor clinical outcome in lung adenocarcinoma. Cancer Biol Ther. 2016;17(3):237-245. doi:10.1080/15384047.2016.1139235 4 Patil T, Mushtaq R, Marsh S, et al. Clinicopathologic characteristics, treatment outcomes, and acquired resistance patterns of atypical EGFR mutations and HER2 alterations in stage IV non-small-cell lung cancer. Clin Lung Cancer. 2020;21(3):e191-e204. doi:10.1016/j.cllc.2019.11.008 5 Fabrizio FP, Attili I, de Marinis F. Uncommon and Rare EGFR Mutations in Non-Small Cell Lung Cancer Patients with a Focus on Exon 20 Insertions and the Phase 3 PAPILLON Trial: The State of the Art. Cancers. 2024; 16(7):1331. https://doi.org/10.3390/cancers16071331 6 Yang JC, Sequist LV, Geater SL, et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015;16(7):830-838. doi:10.1016/S1470-2045(15)00026-1 7 GILOTRIF® (afatinib tablets), for oral use [package insert]. Boehringer Ingelheim Pharmaceuticals, Inc.; 2022. 8 Moores SL, Chiu ML, Bushey BS, et al. A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res. 2016;76(13):3942-3953. doi:10.1158/0008-5472.CAN-15-2833 9 Vijayaraghavan S, Lipfert L, Chevalier K, et al. Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet Bispecific Antibody, Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis. Mol Cancer Ther. 2020;19(10):2044-2056. doi:10.1158/1535-7163.MCT-20-0071 10 Yun J, Lee SH, Kim SY, et al. Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020;10(8):1194-1209. doi:10.1158/2159-8290.CD-20-0116 11 Asia-Pacific practical consensus in the management of adverse events related to amivantamab-based therapies in non-small cell lung cancer. Lung Cancer. Published online May 22, 2026. doi:10.1016/S0169-5002(26)00466-6. 12 RYBREVANT® Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 13 ClinicalTrials.gov. A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). Available at: https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed May 2026. 14 The World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed May 2026. 15 American Cancer Society. What is Lung Cancer? https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html. Accessed May 2026. 16 Oxnard JR, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013 Feb;8(2):179-84. doi: 10.1097/JTO.0b013e3182779d18. 17 Bauml JM, et al. Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real World Datasets. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 18 Pennell NA, et al. A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol. 37:97-104. 19 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 20 Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. 21 Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res. 2015;5(9):2892-2911. 22 American Lung Association. EGFR and Lung Cancer. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr. Accessed May 2026. 23 Howlader N, et al. SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site. 24 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65. 25 Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013 Feb; 12(2):220-9. 26 Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 27 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3.2026 © National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed May 2026. 28 Cho BC, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR-mutated advanced non-small-cell lung cancer: Results From LASER301. J Clin Oncol. 2023;41(26):4208-4217. 29 LAZCLUZE® Prescribing Information. Horsham, PA: Janssen Biotech, Inc. The content above comes from the network. if any infringement, please contact us to modify.

临床试验资讯研究交流群（点击） 每年，美国临床肿瘤学会（ASCO）都会根据最新的研究证据更新晚期肺癌的治疗指南。2026年的更新版本已经发布，无论肿瘤有没有检测到驱动基因突变，都可能有新的治疗选项值得了解。今天癌度用通俗的语言，帮大家梳理这份新指南中最重要的变化——哪些新药被写进了推荐，哪些联合方案成为了新的标准，以及这些变化对患者和家属意味着什么。 本文参考文献刊例示意图 一、没有驱动基因突变的患者：免疫治疗家族新增成员 对于没有EGFR、ALK、ROS1等驱动基因突变的晚期非小细胞肺癌患者，免疫治疗联合化疗一直是标准的一线方案。2026年指南更新中，一个新的PD-1抑制剂retifanlimab正式加入了这个推荐列表。 支持这个推荐的是一项名为POD1UM-304的III期研究，纳入了583名初治晚期患者。结果显示，retifanlimab联合化疗组的总体生存时间中位数达到18.1个月，单纯化疗组只有13.4个月，死亡风险降低约25%；控制疾病不进展的时间也从5.5个月延长到7.7个月，肿瘤明显缩小的患者比例为52%，化疗组为39%。副作用方面以贫血和白细胞降低为主，总体在可控范围内。指南专家组明确指出，retifanlimab的加入主要是为临床提供更多选择，尤其在不同药物的可及性或价格存在明显差异的情况下，患者和医生有了更多空间来做出最合适的决策。 同样值得关注的是PD-1/VEGF双特异性抗体依沃西单抗。一项名为HARMONi-6的研究，将依沃西单抗联合化疗与替雷利珠单抗联合化疗进行了头对头比较，用于肺鳞癌一线治疗，结果显示依沃西组控制疾病不进展的时间达到11.1个月，显著优于对照组的6.9个月，而且无论患者的PD-L1表达高低，都能从中获益。数据相当亮眼，但指南专家组也指出，该研究随访时间偏短，对照组患者特征存在一些差异，因此暂未将依沃西纳入正式推荐。不过它的潜力已经得到认可，后续更完整的数据值得持续关注。 图来自摄图网 二、有驱动基因突变的患者：靶向治疗选项更加丰富 对于检测出特定驱动基因突变的患者，2026年指南在多个靶点上都做了更新。 EGFR经典突变方面，奥希替尼依然是首选方案，但新指南明确指出拉泽替尼作为单药治疗，疗效和安全性与奥希替尼相当，可以作为替代选择。一项头对头研究显示，拉泽替尼组控制疾病不进展的时间为18.5个月，奥希替尼组为16.6个月，两者没有显著差异，副作用谱也类似，主要是腹泻和皮疹。对于因各种原因无法使用奥希替尼的患者，这是一个经过验证的备选方案。 EGFR非经典突变（如G719X、L861Q、S768I等）过去的治疗选择相对有限。新的证据支持埃万妥单抗联合拉泽替尼作为一线选择，一项单臂研究显示初治患者控制疾病不进展的时间达到19.5个月，肿瘤明显缩小的患者比例为57%，是相当不错的数据。需要提醒的是，这个联合方案的副作用较为明显，超过70%的患者出现了3级以上的不良事件，皮疹、甲沟炎、输液反应和静脉血栓是需要重点关注和预防的问题，用药期间需要做好皮肤护理，并预防性使用抗凝药物。 EGFR 20号外显子插入突变方面，指南继续推荐化疗联合埃万妥单抗，舒沃替尼用于后线治疗。 其他驱动基因的推荐也有更新，逐一简要说明。 ALK融合的患者，阿来替尼、布格替尼、洛拉替尼均为一线强推荐，耐药后根据此前用药情况选择洛拉替尼等后线方案。 ROS1融合的患者，一线可选克唑替尼、恩曲替尼、瑞普替尼或他雷替尼。 MET基因14号外显子跳跃突变，卡马替尼或替泊替尼为一线首选。 BRAF基因V600E突变，推荐达拉非尼加曲美替尼或恩考芬尼加比美替尼的双靶方案。 RET融合，塞尔帕替尼为首选。 KRAS基因G12C突变，索托拉西布或阿达格拉西布用于化疗或免疫治疗后的后线治疗。 HER2突变，德曲妥珠单抗（DS-8201）、宗格替尼或泽瓦替尼均为后线可选项。 三、对患者和家属最重要的几点启示 从这次指南更新中，有几个值得患者和家属认真对待的方向。 第一，对于没有驱动基因突变的患者，免疫治疗的可选方案在扩大，retifanlimab的加入让医患双方有了更大的选择空间；而依沃西单抗虽然尚未正式写入推荐，但已经展现出"正面击败标准方案"的数据，值得持续关注后续进展。 第二，对于有驱动基因突变的患者，靶向治疗正在变得越来越精细。除了经典的奥希替尼，现在有了拉泽替尼这个等效替代；非经典EGFR突变有了双靶联合方案；其他靶点的可选药物也在增多，耐药后的后线选择也在逐步完善。 第三，指南再次强调，所有晚期患者都应该进行全面的多基因检测，包括组织样本和血液样本，DNA和RNA两个层面都要覆盖，避免遗漏潜在的靶向治疗机会。PD-L1免疫组化的结果也不应单独作为治疗决策的唯一依据。 第四，对于标准治疗失败或携带罕见突变的患者，积极向主治医生咨询是否有匹配的临床试验，往往是获得更新、更有潜力的治疗方案的最快途径。 写在最后 精准治疗时代，晚期肺癌的治疗格局正在持续改变。每一次指南更新的背后，都是一项项临床研究真实数据的积累。了解最新的推荐变化，有助于患者和家属与主治医生进行更有针对性的沟通，结合自身的基因突变类型、身体状况和实际情况，制定最适合自己的方案。 关注癌度，我们持续追踪国际指南更新和肺癌新药进展。如果您有基因检测报告需要解读，或想了解是否有匹配的临床试验，欢迎在微信扫描下图的二维码联系我们。 2026年福利 “吉爱3000”惠民检项目，最低2000+可及的二代基因检测专属福利，详情微信扫码进行基因检测报告解读、申请新药临床试验！ 参考文献： ASCO Clinical Practice Guideline Update: Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer, Journal of Clinical Oncology, 2026.  往期推荐 一个分子，三重打击！国产三特异性抗体SCTB41，为免疫耐药患者打开新门! PD-1耐药后还有新出路？全球唯一双抗LBL-024，一脚刹车一脚油门，冷肿瘤也能“燃”起来! 确诊肺癌后还没来得及手术，肿瘤居然自己消失了？这个真实病例，让人既震惊又深思! 刚刚，中国双抗登顶ASCO全体大会！肺鳞癌死亡风险直降34%，胰腺癌一线临床同步启动! 点赞 收藏 分享 点亮小手爱心，送来温暖鼓励