A Phase 2b, Open-Label, Two-cohort Study of Subcutaneous Amivantamab in Combination With Lazertinib as First-Line Treatment, or Subcutaneous Amivantamab in Combination With Platinum-Based Chemotherapy as Second-line Treatment, for Common EGFR-Mutated Locally Advanced or Metastatic NSCLC

The primary purpose of the study is to assess how well amivantamab subcutaneous (SC) administration in combination with lazertinib or in combination with chemotherapy works (antitumor activity) in participants with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC; that is one of the major types of lung cancer).

开始日期2024-11-25

申办/合作机构

Janssen Research & Development LLC

KCT0009698 / RecruitingN/AIIT

The first line Lazertinib treatment for metastatic EGFRm NSCLC; the real world evidence in South Korea

开始日期2024-08-29

申办/合作机构

Hallym University Medical Center

KCT0008774 / Recruiting临床2期IIT

A randomized, phase 2 trial of lazertinib and chemotherapy combination in EGFR-mutant NSCLC patients without ctDNA clearance after lead-in lazertinib monotherapy (CHAMELEON)

开始日期2024-08-01

申办/合作机构

Yonsei University Severance Hospital

100 项与甲磺酸兰泽替尼相关的临床结果

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100 项与甲磺酸兰泽替尼相关的转化医学

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100 项与甲磺酸兰泽替尼相关的专利（医药）

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项与甲磺酸兰泽替尼相关的文献（医药）

2024-10-20·JOURNAL OF CLINICAL ONCOLOGY

Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study

Article

作者: Liu, Baogang ; Gamil, Mohamed ; Zer, Alona ; Silva Melo Cruz, Felipe José ; Suksombooncharoen, Thatthan ; Moore, Sara ; Teixeira, Encarnação ; Moskovitz, Mor ; Akamatsu, Hiroaki ; Prasongsook, Naiyarat ; Sendur, Mehmet Ali Nahit ; Liang Tan, Jiunn ; Lee, Se-Hoon ; Voon, Pei Jye ; Urban, Damien ; Novello, Silvia ; Nguyen, Danny ; Bleckmann, Annalen ; Vergnenègre, Alain ; Haddish-Berhane, Nahor ; Nagrial, Adnan ; Bauml, Joshua M. ; Hsu, Ping-Chih ; Erdem, Dilek ; Lorenzini, Patricia ; Greystoke, Alastair ; Sabari, Joshua K. ; Cappuzzo, Federico ; Emde, Till-Oliver ; Hung, Jen-Yu ; John, Thomas ; Şendur, Mehmet Ali Nahit ; Joshi, Rohit ; Tota, Rajanikar ; Kondo, Masashi ; Ramos, Elisa F. ; Baig, Mahadi ; Li, Juan ; Leighl, Natasha ; Kowalski, Dariusz ; Estevinho, Fernanda ; da Silva, Flavio Ferreira ; Cheng, Ying ; Danchaivijitr, Pongwut ; Garcia Campelo, Maria del Rosario ; Lim, Sun Min ; Wainsztein, Vanina ; Massutí, Bartomeu ; Spira, Alexander I. ; Seng-Hooi Low, John ; Greillier, Laurent ; Ozyilkan, Ozgur ; Ji, Mei ; Tamiya, Motohiro ; Alhadab, Ali ; Lin, Sheng-Hao ; Leighl, Natasha B. ; Liu, Caigang ; Salinas, Jorge ; Kim, Young-Chul ; Wang, Jialei ; Sanborn, Rachel E. ; Peled, Nir ; Han, Ji-Youn ; Teixeira, Encarnacao ; Clemens, Pamela L. ; Cortot, Alexis ; Marmarelis, Melina E. ; Ghosh, Debopriya ; Lurdes Ferreira, Maria ; Minchom, Anna R. ; Ohe, Yuichiro ; Nahit Sendur, Mehmet Ali ; Özgüroğlu, Mustafa ; Passaro, Antonio ; Cho, Byoung Chul ; Yoshioka, Hiroshige ; Korbenfeld, Ernesto ; Qin, Angel ; Zurawski, Bogdan ; Felip, Enriqueta ; Alexander, Mariam ; Xie, John ; Cil, Timucin ; Wehler, Thomas ; Verheijen, Remy B. ; Chih-Hsin Yang, James ; Zhao, Yanqiu ; José Silva Melo Cruz, Felipe

PURPOSE:

Phase III studies of intravenous amivantamab demonstrated efficacy across epidermal growth factor receptor ( EGFR )–mutated advanced non–small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy.

PATIENTS AND METHODS:

Patients with EGFR -mutated advanced NSCLC who progressed after osimertinib and platinum-based chemotherapy were randomly assigned 1:1 to receive subcutaneous or intravenous amivantamab, both combined with lazertinib. Coprimary pharmacokinetic noninferiority end points were trough concentrations (C trough ; on cycle-2-day-1 or cycle-4-day-1) and cycle-2 area under the curve (AUC D1-D15 ). Key secondary end points were objective response rate (ORR) and progression-free survival (PFS). Overall survival (OS) was a predefined exploratory end point.

RESULTS:

Overall, 418 patients underwent random assignment (subcutaneous group, n = 206; intravenous group, n = 212). Geometric mean ratios of C trough for subcutaneous to intravenous amivantamab were 1.15 (90% CI, 1.04 to 1.26) at cycle-2-day-1 and 1.42 (90% CI, 1.27 to 1.61) at cycle-4-day-1; the cycle-2 AUC D1-D15 was 1.03 (90% CI, 0.98 to 1.09). ORR was 30% in the subcutaneous and 33% in the intravenous group; median PFS was 6.1 and 4.3 months, respectively. OS was significantly longer in the subcutaneous versus intravenous group (hazard ratio for death, 0.62; 95% CI, 0.42 to 0.92; nominal P = .02). Fewer patients in the subcutaneous group experienced infusion-related reactions (IRRs; 13% v 66%) and venous thromboembolism (9% v 14%) versus the intravenous group. Median administration time for the first infusion was reduced to 4.8 minutes (range, 0-18) for subcutaneous amivantamab and to 5 hours (range, 0.2-9.9) for intravenous amivantamab. During cycle-1-day-1, 85% and 52% of patients in the subcutaneous and intravenous groups, respectively, considered treatment convenient; the end-of-treatment rates were 85% and 35%, respectively.

CONCLUSION:

Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced IRRs, increased convenience, and prolonged survival.

2024-10-01·JAMA Oncology

The Role of Lazertinib in Patients With EGFR-Variant Non–Small Cell Lung Cancer

Article

作者: Cheng, Haiying

2024-10-01·JAMA Oncology

Lazertinib in EGFR-Variant Non–Small Cell Lung Cancer With CNS Failure to Prior EGFR Tyrosine Kinase Inhibitors

Article

作者: Kang, Jin Hyoung ; Kim, Dong-Wan ; Kim, Hye Ryun ; Kim, Sangwoo ; Kim, Yu Jung ; Choi, Yoon Ji ; Hong, Min Hee ; Kim, Ju Won ; Youk, Jeonghwan ; Ahn, Hee Kyung ; Hwang, Shinwon ; Kim, Tae Min ; Lim, Sun Min ; Keam, Bhumsuk

Importance:

EGFR-variant non–small cell lung cancer (NSCLC) is associated with a high rate of central nervous system (CNS) metastases, even with treatment with first-generation or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).

Objective:

To investigate CNS activity with lazertinib, a third-generation EGFR TKI.

Design, Setting, and Participants:

This multicenter single-arm, phase 2 nonrandomized controlled trial was conducted in South Korea and included patients with EGFR-variant NSCLC who had asymptomatic or mildly symptomatic brain metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs. Data were collected from June 2021 to April 2022, with a data cutoff date of December 15, 2022.

Exposure:

Lazertinib, 240 mg, once daily.

Main Outcomes and Measures:

The primary end point was intracranial objective response rate (iORR) in the evaluable population according to the Response Evaluation Criteria in Solid Tumours version 1.1 assessed by the investigators. Secondary end points included intracranial progression-free survival (iPFS) and iORR in patients with T790M-negative disease and isolated CNS progression as well as overall ORR, duration of response, intracranial duration of response, disease control rate, overall survival, cerebrospinal fluid penetration of lazertinib, and safety.

Results:

Among 40 included patients, 25 (63%) were women, and the median (range) age was 63 (29-85) years. A total of 38 patients were evaluable for tumor response, including 12 patients with leptomeningeal metastases. At data cutoff, the median (range) follow-up was 13.6 (2.9-17.7) months. The iORR for the evaluable population was 55% (21 of 38; 95% CI, 38.3-71.4); for patients with T790M-positive disease, 80% (4 of 5; 95% CI, 28.4-99.5); for patients with T790M-negative disease, 43% (9 of 21; 95% CI, 21.8-66.0); and for patients with T790M-unknown disease, 67% (8 of 12; 95% CI, 34.9-90.1). The median iPFS was 15.8 months (95% CI, 15.2-not reached) for the evaluable population, 15.2 months (95% CI, 4.2-not reached) for the T790M-positive subgroup, 15.4 months (95% CI, 7.9-not reached) for the T790M-negative subgroup, and 18.0 months (95% CI, 3.9-not reached) for the T790M-unknown subgroup. The cerebrospinal fluid penetration rate of lazertinib was 46.2% (95% CI, 10.0-49.6), providing further support for its mechanism of intracranial response. Most adverse events were grade 1 or 2.

Conclusions and Relevance:

In this study, lazertinib had substantial CNS activity, regardless of T790M status, against the progression of intracranial metastases with or without leptomeningeal metastases after unsuccessful treatment with first-generation or second-generation EGFR TKIs in patients with metastatic EGFR-variant NSCLC. These results suggest that using lazertinib instead of brain local treatment could be a potential strategy in patients with EGFR-variant NSCLC whose CNS metastases progressed after prior EGFR TKI treatment.

Trial Registration:

ClinicalTrials.gov Identifier: NCT05326425

230

项与甲磺酸兰泽替尼相关的新闻（医药）

2024-11-15

·Firstwordpharma

Mixed bag of recommendations in latest CHMP update

The European Medicine Agency's drug advisory panel recommended the approval of several new medicines on Friday, but also issued a negative opinion on a pair of drugs. The most notable therapy to receive a nod from the Committee for Medicinal Products for Human Use (CHMP) was Eisai and Biogen’s Alzheimer's disease drug Leqembi (lecanemab), reversing an earlier thumbs-down. Joining Leqembi in the greenlit group are Bristol Myers Squibb's Augtyro (repotrectinib), InflaRx's Gohibic (vilobelimab) and Johnson & Johnson's Lazcluze (lazertinib).Augtyro, a next-generation tyrosine kinase inhibitor (TKI), was recommended for adults with ROS1-positive advanced non–small-cell lung cancer (NSCLC), as well as for adults and paediatric patients ages 12 years and older with advanced solid tumours expressing a NTRK gene fusion. The FDA in June granted the drug a tumour-agnostic approval to treat solid cancers harbouring NTRK gene fusions.InflaRx's product is a human complement factor C5a-targeting monoclonal antibody (mAb) designed to control inflammatory response-driven tissue and organ damage. The CHMP recommended its use in adults with acute respiratory distress syndrome (ARDS) due to COVID-19 who are receiving systemic corticosteroids and receiving invasive mechanical ventilation. The mAb was given Emergency Use Authorisation by the FDA in April 2023. J&J's CHMP nod covers the combination of Lazcluze with Rybrevant (amivantamab-vmjw) to treat first-line, advanced NSCLC in adults with EGFR exon 19 deletions or exon 21 L858R substitution mutations. The former is an EGFR tyrosine kinase inhibitor and the latter is an EGFR/MET-targeting bispecific.The duo was approved by the FDA in August for frontline NSCLC, where it is seeking to displace AstraZeneca's Tagrisso (osimertinib) as the market leader (see – Spotlight On: Experts sceptical that J&J can challenge AstraZeneca's dominance of the EGFRm lung cancer market).Those receiving negative CHMP opinions include Legacy Healthcare's herbal hair loss hopeful Cinainu (allium/citrus/paullinia/cacao) and Orphelia Pharma's chemotherapy temozolomide for neuroblastoma.

上市批准加速审批免疫疗法

2024-11-11

·医药魔方Info

制药巨头双抗业务版图

ADC热潮之后，很多制药巨头在布局前沿技术赛道时瞄准了一个共同的方向——双抗。根据医药魔方数据库，2024年前9个月，全球药企围绕双抗药物达成了31笔交易，数量上比之前三年的每一年都要多。这其中也不乏制药巨头的重量级押注。8月，默沙东以7亿美元的首付款将同润生物一款处于I期阶段的CD3/CD19双抗CN201收入囊中。7月，诺华与Dren Bio就髓系细胞募集双抗的开发达成合作，交易总额达30亿美元。与此同时，一些药企也在加快双抗药物的临床开发布局。比如阿斯利康在今年接连启动了TIGIT/PD-1双抗rilvegostomig的4项注册性临床试验，包括联合化疗对比K药的III期头对头研究。更早下注的玩家已经步入收获。比如，罗氏的眼科双抗法瑞西单抗已成为其业绩增长的核心驱动，上市第2年的销售额便轻松突破25亿美元。强生的埃万妥单抗则在研发端实现了重要突破，联合兰泽替尼头对头击败奥希替尼，并借此拓展了新适应症。本文对制药巨头的双抗产品管线进行梳理，并对管线较丰富的几家企业进行分析，揭示它们不同的布局重点与扩张策略。制药巨头双抗产品及临床管线罗氏：打造畅销产品，站上赛道制高点在双抗赛道，罗氏已展现王者风采，强大的已上市产品阵容就是其实力的最好印照。根据医药魔方数据库，全球共有15款双抗获批上市，罗氏独占4款，与Genmab并列为全球拥有最多上市双抗产品的药企。不仅仅是数量上的领先，这些产品的商业化成绩亦斐然。立足于已有产品，罗氏徐徐铺开布局版图。艾美赛珠单抗是首个非凝血因子类血友病药物，可每4周皮下给药一次。它巧妙地利用双抗的作用模式，同时结合凝血因子IXa（FIXa）和FX来模拟FVIII的凝血功能。凭借创新性与变革性治疗价值，艾美赛珠单抗逐步“征服”广大患者，销售额一路攀升，2024上半年创收21.43亿瑞士法郎（约合24.21亿美元），是全球销售额最高的双抗药物。新一代FX/FIXa双抗RG6512也已推进至I/II期临床阶段，其与FIX和FX形成三元复合物的能力显著优于艾美赛珠单抗，有望以更低的剂量和更长的给药间隔实现突破。继罗氏之后，诺和诺德也看好血友病双抗的开发前景。Mim8的III期研究已传来捷报，预计年内申报上市。在血液疾病领域，罗氏还先后推出了两款CD3/CD20双抗莫妥珠单抗和格菲妥单抗，形成差异化布局。莫妥珠单抗被设计成典型的1:1结构，疗效相对温和，更适用于惰性淋巴瘤，而格菲妥单抗具有2:1比例的CD20与CD3结合位点，对表达CD20的恶性B细胞产生更强的靶向作用，可以攻克侵袭性和难治淋巴瘤。除淋巴瘤外，罗氏还希望借力双抗打破多发性骨髓瘤（MM）的现有格局。针对发病率第二高的血液肿瘤，与多数企业押注CD3/BCMA双抗不同，罗氏主要将希望寄托于FCRH5/CD3双抗cevostamab和GPRC5D/CD3双抗forimtamig。I/II期CAMMA 2研究显示，cevostamab针对三重难治性MM患者的总缓解率（ORR）为67%。法瑞西单抗是当下罗氏增长势头最强劲的双抗产品。今年上半年，法瑞西单抗销售收入几近翻倍，达17.94亿瑞士法郎（+93%，约20.27亿美元），未来销售峰值或将超越巅峰时期的阿柏西普。法瑞西单抗的成功不是偶然，这依赖于罗氏在眼科赛道的深厚底蕴，此前罗氏已打造出全球首个应用于眼科的抗血管内皮生长因子（VEGF）药物雷珠单抗。法瑞西单抗同时靶向VEGF-A和血管生成素2（Ang-2）两条不同的信号通路，获批了湿性年龄相关性黄斑变性（wAMD）、糖尿病黄斑水肿（DME）和视网膜静脉阻塞（RVO）继发黄斑水肿三大适应症。与单纯抗VEGF疗法相比，法瑞西单抗显著减少了眼部注射给药频率，只需每4个月给药1次。眼科赛道，罗氏继续向着“进一步提高护理标准”的战略目标前进。两款靶向VEGF的双抗应运而生。下一代Ang2/VEGF-A双抗zifibancimig采用港式给药系统（PDS）尝试进一步延长nAMD治疗间隔；VEGF/IL-1β双抗经玻璃体内给药，用于治疗RVO继发黄斑水肿。罗氏在实体瘤领域推进最快的双抗是靶向PD-1/LAG-3的tobemstomig，处于II期临床阶段。PD-1与LAG-3的协同作用已经得到充分验证，BMS的双免疗法Opdualag于2022年3月获批上市。围绕tobemstomig，罗氏重点开启了一项单药或联合TIGIT单抗tiragolumab一线治疗尿路上皮癌的注册性临床（NCT05645692）。另有三款CD3双抗夯实罗氏在实体瘤领域的布局。CD3/HER2靶向的runimotamab主攻乳腺癌和胃癌；CD3/GPC3靶向的ERY974在探索治疗肝细胞癌的可行性；CD3/CLDN6靶向的SAIL66具备FIC潜质，CLDN6靶点尚未成药，其开发过程必定充满挑战，今年7月安进已终止开发同靶点双抗AMG 794。双抗的身影也出现在罗氏的神经科学布局中。Aβ/TfR靶向的trontinemab是罗氏在阿尔茨海默病领域的一次大胆创新。从作用机制上，trontinemab就体现出了与众不同之处，它运用罗氏大脑穿梭技术（brainshuttle），将靶向Aβ的单抗（gantenerumab）与可以和转铁蛋白受体1（TfR1）相结合的蛋白域融合，通过TfR1介导的胞吞转运有效协助抗体穿越血脑屏障。早期临床数据显示，与标准Aβ单抗相比，trontinemab能以相对较低的剂量（1.8和3.6mg/kg）快速且稳健地减少淀粉样蛋白斑块。手握如此丰富的产品管线，罗氏已率先占据双抗赛道的竞争高地。在不断地开疆拓土中，罗氏还将继续扩大优势。强生：血液肿瘤、实体瘤、自免全面出击近几年，强生以每年推出1款产品的速度在双抗赛道强势崛起。2021年5月，全球首款c-Met/EGFR双抗埃万妥单抗在美获批EGFR外显子20插入突变非小细胞肺癌（NSCLC）适应症，其只需5分钟给药的皮下剂型也已申报上市。埃万妥单抗正在抢占奥希替尼的市场份额，后者2024上半年销售额达32亿美元。MARIPOSA研究中，埃万妥单抗联合兰泽替尼头对头击败奥希替尼，显示出一线治疗EGFR外显子19缺失或外显子21 L858R置换突变NSCLC的PFS获益。MARIPOSA-2研究则聚焦奥希替尼耐药后的未满足需求。凭借这两项研究，埃万妥单抗接连拓展了2项新适应症。 2022年8月，全球首款CD3/BCMA双抗特立妥单抗首次在欧盟获批上市；一年后，全球首款CD3/GPRC5D双抗塔奎妥单抗也问世了。这两款双抗是强生统治MM业务的重要接力产品。在MM领域，强生早已建立了霸主地位，从FIC蛋白酶体抑制剂硼替佐米到全球首款CD38单抗达雷妥尤单抗，再到BCMA CAR-T西达基奥仑赛和双抗，产品护城河深厚，持续引领着MM治疗手段的演变。MM这块大蛋糕也有很多玩家竞争，仅双抗这一类型药物的相关管线就达到65项，辉瑞的CD3/BCMA双抗elranatamab已经获批上市。对于后续的双抗药物储备，强生着重开辟实体瘤，前列腺癌是强生下一个进攻方向。靶向CD3/PSMA的JNJ-8114、靶向CD3/KLK2的JNJ-8343、靶向PSMA/CD28的JNJ-9401都已进入临床阶段。不过JNJ-8114的一项I期研究（NCT05441501）在今年3月刚刚完成，但却已消失在强生2024Q1的管线图中。此前，强生还放弃了另一款治疗前列腺癌的CD3/TMEFF2双抗管线JNJ-8902。 JNJ-8343建立在强生和Zymeworks 2017年的合作基础上。交易背后，强生看中了Zymeworks的Azymetric和EFECT平台，其中Azymetric平台通过对IgG样抗体的重链和轻链进行专有的氨基酸修饰，从而实现单抗到多抗的转换。 JNJ-9401同样诞生于合作模式。2021年10月，强生与Xencor就CD3/CD20双抗plamotamab和CD28双抗达成一笔超13亿美元的交易。不过并不是所有交易都能走到最后。今年6月，强生已经退回了plamotamab的全球权益。至于CD28双抗的开发，除JNJ-9401外，还延伸出了CD28/CD20双抗JNJ-1493这一产品，剑指非霍奇金淋巴瘤（NHL）领域。靶向CD3/CD22的JNJ-8780也主要用于NHL，强生于2020年9月启动了该药物的首次临床试验（NCT04540796）。2022年9月，JNJ-8780的临床足迹扩张至中国，然而在2023年10月强生主动终止了这一研究（CTR20222211）。事实上，之后强生仍开展了有关JNJ-8780的临床试验，不过主要作为联合的选项出现。2023年11月，强生启动了JNJ-1493联合JNJ-8780或CD3/CD20/CD79b三抗JNJ-8543的试验（NCT06139406）。双抗+双抗甚至三抗的组合，还是一个待验证的新方向，也期待强生的突破。血液疾病领域，强生还布局了一款潜在FIC双抗JNJ-9968，用于治疗骨髓纤维化。该药物靶向CD3/CALR，而CALR（钙网蛋白）是一个极其新颖的未成药靶标，全球在研药物也仅有4款。有研究[1]证实，暴露在表面的CALR可以作为NK细胞的内源性激活剂，向骨髓细胞传递强大的促吞噬信号，协调先天免疫监视的各个方面。在自免领域，强生也扎下了较深的根基，乌司奴单抗、英夫利昔单抗、古赛奇尤单抗、戈利木单抗等生物制剂每年为其带来了可观的业绩增量。从药物类型来看，这些产品都属于单抗，自免领域双抗药物的迭代也在推进中。靶向IL-4Rα/IL-31的NM26治疗特应性皮炎（AD）的I期研究于2023年5月启动。一年后，强生又以8.5亿美元现金收购了聚焦于免疫学的Proteologix，目的就是丰富自免双抗管线。收购而来的IL-13/TSLP双抗PX128和IL-13/IL-22双抗PX130均处于临床前阶段，两者主要适应症都覆盖了AD。针对AD，强生全球免疫疗法负责人David Lee认为双抗有“实现最佳疾病疗效的机会”[2]。AD是一种异质性疾病，不同的患者亚群有不同的致病通路，“目前的AD疗法要么仅能抑制单一致病通路且疗效有限，要么具有广泛的免疫抑制作用，但又会导致严重的安全性问题”，而双抗可以同时针对两种不同的致病通路，可能提供高标准疗效和缓解。强生在双抗赛道的布局，策略性覆盖了实体瘤、血液学和自免领域这几个优势业务板块。目标明确，火力集中，如此步步为营之下，强生的收获是必然的。阿斯利康：倾力打造肿瘤免疫双抗“双子星” 阿斯利康在双抗赛道上的布局渐近收获期。靶向PD-1/CTLA-4的volrustomig和靶向TIGIT/PD-1的rilvegostomig这两款肿瘤免疫（IO）双抗均已进入III期临床阶段，共同瞄准NSCLC大适应症，也是阿斯利康着重打造的“双子星”。在肺癌领域，阿斯利康凭借一个个重磅产品持续引领着临床治疗变革，从一代EGFR-TKI吉非替尼到三代的奥希替尼，PD-L1单抗度伐利尤单抗和HER2 ADC德曲妥珠单抗肺癌适应症的快速拓展，又不断稳固阿斯利康肺癌领导者的地位。阿斯利康与第一三共合力打造的TROP2 ADC药物Dato-DXd也已申报上市，尝试覆盖非鳞状NSCLC人群。有了小分子、单抗、ADC不同类型的产品之后，阿斯利康并没有停止对新技术的追逐，而且它希望立足现有产品基础打出一套更强的组合拳。双抗就是阿斯利康实现上述目标的重要资产。透视现有的临床布局，可以发现阿斯利康为IO双抗开辟的版图主要围绕联合治疗展开。一方面是IO双抗与化疗的联合，可能实现比PD-1单抗更强的疗效。2023年10月，阿斯利康启动了volrustomig联合化疗一线治疗PD-L1表达＜50%的NSCLC的III期研究（NCT05984277），头对头K药。今年10月，阿斯利康又登记了rilvegostomig联合化疗一线治疗PD-L1阳性的非鳞状NSCLC的III期头对头研究（NCT06627647），同样对标K药。在挑战K药的道路上，已经有先行者取得胜利。在一线治疗PD-L1阳性NSCLC的III期HARMONi-2研究中，康方生物的PD-1/VEGF双抗依沃西单抗相较于K药实现了更显著的PFS获益。另一方面，阿斯利康倾力挖掘更具竞争力的“IO+ADC”组合。比如，rilvegostomig与Dato-DXd的联用。围绕该组合，阿斯利康已先后启动TROPION-Lung10和TROPION-Lung12两项III期研究，分别针对一线治疗PD-L1高表达的非鳞状NSCLC和辅助治疗IB-IIIB期NSCLC场景。此外，靶向PD-1/TIM-3的sabestomig和靶向EGFR/c-Met的FPI-2053也可能有治疗NSCLC的潜力。Sabestomig已读出单药二线治疗IIIB-IV期NSCLC的I/IIa期研究数据（NCT04931654），19例患者中有2例实现未确认的部分缓解（PR）。值得一提的是，上述双抗不仅在阿斯利康的肺癌布局中扮演重要角色，也是其进击消化道肿瘤领域的潜在利器。II期GEMINI-Gastric研究显示，接受rilvegostomig联合化疗治疗的40例HER2阴性胃或胃食管交界腺癌患者的确认ORR为52.5%。靶向CD3/CLDN18.2的AZD5863（HBM7022）主攻胃癌、食管癌和胰腺癌等，由阿斯利康于2022年4月从和铂医药引进来的，交易时其还处于临床前开发阶段。“通过临床前资料，我们发现HBM7022在包括胃癌和胰腺癌在内的实体瘤中表现出强大的潜在功效。”阿斯利康肿瘤研发负责人Susan Galbraith当时表示。敢于在早期就出手押注，也充分说明阿斯利康对于这款中国创新资产的看好。在实体瘤领域之外，阿斯利康也有两款双抗已推进至III期临床阶段，即gefurulimab和AZD0486。开发gefurulimab的主要目的是为涉及末端补体途径激活的慢性疾病患者提供皮下治疗选择。这是一种迷你双抗（25kD），由一个N端白蛋白结合型VHH和一个C端C5结合型VHH通过柔性linker连接而成。如此设计的巧妙之处在于，较小的分子量可以带来更好的渗透性，与白蛋白的结合能够延长其半衰期。 CD3/CD19靶向的AZD0486由阿斯利康以超12亿美元收购TeneoTwo获得。通过单药或联合BTK抑制剂、CD20靶向疗法治疗，AZD0486有望解锁滤泡性淋巴瘤（FL）、弥漫性大B细胞淋巴瘤（DLBCL）等血液肿瘤适应症。今年8月，阿斯利康已经启动AZD0486联合CD20单抗利妥昔单抗一线治疗FL的III期试验（NCT06549595），计划招募1005例患者。随着4款不同作用机制的双抗管线相继进入III期临床阶段，阿斯利康已经成为双抗赛道上实力不容小觑的明星玩家。结合联合治疗的策略打法，这些双抗可能将与更多已上市产品形成紧密捆绑的关系，为未来的市场竞争做好铺垫。参考资料： [1]Jitka Fucikova, Radek Spisek, et al. Calreticulin and cancer[J]. Cell Research volume 31, pages5–16 (2021) [2]https://www.jnj.com/media-center/press-releases/johnson-johnson-to-acquire-proteologix-inc-to-lead-in-atopic-dermatitis-treatment 推荐阅读安进双抗业务布局的启示制药巨头的核药版图制药巨头ADC布局：辉瑞有钱任性，罗氏抢占先机，AZ异军突起，默沙东雄心勃勃...... Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

临床3期引进/卖出财报抗体药物偶联物临床1期

2024-11-05

·PRNewswire

J INTS BIO Launches AI-Supercomputing Alliance to Transform Cancer Therapy

- Yuhan Corporation CEO Wook Je Cho, National Assembly Member Seong Hoon Park, and KAIST Professor Joung Ho Kim join a pioneering collaboration in precision oncology. SEOUL, South Korea, Nov. 5, 2024 /PRNewswire/ -- On November 4, 2024, J INTS BIO hosted a significant MOU signing ceremony at Baekyangnuri Plaza, Yonsei University, unveiling a groundbreaking AI-driven collaboration to revolutionize cancer treatment. This ambitious alliance unites leading institutions, including Yonsei University College of Medicine's DAAN Cancer Research Institute, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Korea Research Institute of Chemical Technology (KRICT), and KAIST. The event featured a distinguished lineup, with Yuhan Corporation CEO Wook Je Cho, National Assembly Representative Seong Hoon Park, and KAIST's Professor Joung Ho Kim, a prominent member of the National AI Committee, highlighting the extensive support from both government and industry sectors. Continue Reading (Photo. From left) Professor Woo Kyung Yu of DGIST, Professor Joung Ho Kim of KAIST, CEO Wook Je Cho of Yuhan Corporation, Professor Byoung Chul Cho of Severance Hospital, Director Seong Kyoon Choi of DGIST, Director Kwang Rok Kim of KRICT, CEO Anna Jo of J INTS BIO, Seong Hoon Park of National Assembly Member, and Senior Researcher Gwang Ho Lee of KRICT (PRNewsfoto/J INTS BIO) Precision Medicine Redefined: AI Meets Multi-Omics J INTS BIO is at the forefront of developing personalized lung cancer therapies through the integration of artificial intelligence and multi-omics technology. Multi-omics offers a comprehensive approach to disease biology by combining genomics, transcriptomics, metabolomics, and proteomics. Using AI and national supercomputing infrastructure, the project aims to enhance drug efficacy prediction and minimize toxicity, addressing the critical challenges that plague conventional oncology drug development. Professor Byoung Chul Cho of Severance Hospital, a key figure behind the development of the highly successful lung cancer drug "Leclaza," emphasized, "AI is revolutionizing precision medicine. By employing AI and supercomputing, we can achieve ultra-precise analysis of patient tissue and genetic profiles, enabling the design of highly effective, personalized treatment strategies." KAIST's Professor Joung Ho Kim added, "AI's capacity to process immense biological datasets and apply machine learning for patient-specific predictions can drastically reduce clinical trial failure rates and accelerate the entire drug discovery process." End-to-End Research Strategy: From Biopsies to AI-Optimized Therapies The collaboration is structured around a comprehensive, four-phase research strategy: meticulous patient sample collection and preparation, AI-driven protein analysis using supercomputers, synthesis of drug candidates informed by AI insights, and rigorous clinical trials for validation. The DAAN Cancer Research Institute at Yonsei University will lead the first phase, collecting lung cancer tissue and genomic samples and preparing them for AI model development. Using cell and animal models, the institute will validate AI predictions, identify drug resistance mechanisms, and refine algorithms to maximize accuracy. DGIST's Core Protein Resources Center will utilize national supercomputers to simulate protein-drug interactions, conducting high-precision structural analyses and virtual experiments. This work will confirm AI-driven hypotheses and facilitate the design of drugs tailored to the molecular characteristics of cancer. KRICT's Medicinal Bio Research Division will synthesize the AI-recommended drug candidates, subjecting them to thorough pharmacological and toxicological assessments. KRICT Director Kwang Rok Kim remarked, "AI is fundamentally transforming the landscape of drug discovery. It allows us to develop optimized therapeutic compounds faster and with greater safety, delivering unprecedented precision in medicine." J INTS BIO will oversee the entire project, managing clinical trials to validate AI-based predictions and develop clinically proven, patient-specific treatment protocols. This approach aims to expedite the path from laboratory research to market readiness, making advanced cancer therapies more accessible to patients worldwide. A Game-Changer in Oncology: Government and Industry in Harmony This collaboration marks a transformative leap in cancer research, showcasing the potential of merging AI with biotechnology. Seong-Kyoon Choi, Director of DGIST's Core Protein Resources Center, stated, "AI and supercomputing together set a new standard for protein analysis and drug design precision. This partnership is poised to deliver groundbreaking advancements in cancer treatment." National Assembly Member Seong Hoon Park underscored the national importance of this initiative: "The integration of AI and biotech is crucial for elevating South Korea's global competitiveness in the bio-industry. The government will continue to provide unwavering support for these pioneering research efforts." Envisioning a future shaped by precision medicine, J INTS BIO and its partners aim to build extensive cancer data infrastructures, providing a solid foundation for ongoing research and innovation. The consortium plans to unveil interim results from the "AI-Supercomputing-Based Personalized Lung Cancer Therapy" project at a major international conference in the first half of next year, showcasing the project's far-reaching impact and potential. SOURCE J INTS BIO WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

100 项与甲磺酸兰泽替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11980	-	-	DB16216

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
EGFR外显子21替代突变非小细胞肺癌	美国	Janssen Biotech, Inc.	2024-08-19
EGFR 外显子 19 缺失突变型非小细胞肺癌	韩国	Yuhan Corp.	2021-01-18
EGFR-T790M 突变非小细胞肺癌	韩国	Yuhan Corp.	2021-01-18

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
EGFR突变的非小细胞肺癌	申请上市	中国	Janssen-Cilag International NV	2024-01-26
EGFR突变的非小细胞肺癌	申请上市	中国	Shanghai Johnson & Johnson Pharmaceutical Ltd.	2024-01-26
EGFR突变的非小细胞肺癌	申请上市	中国	Janssen-Cilag SpA	2024-01-26
晚期非小细胞肺癌	临床3期	美国	Janssen Research & Development LLC	2022-08-05
晚期非小细胞肺癌	临床3期	中国	Janssen Research & Development LLC	2022-08-05
晚期非小细胞肺癌	临床3期	日本	Janssen Research & Development LLC	2022-08-05
晚期非小细胞肺癌	临床3期	阿根廷	Janssen Research & Development LLC	2022-08-05
晚期非小细胞肺癌	临床3期	澳大利亚	Janssen Research & Development LLC	2022-08-05
晚期非小细胞肺癌	临床3期	巴西	Janssen Research & Development LLC	2022-08-05
晚期非小细胞肺癌	临床3期	加拿大	Janssen Research & Development LLC	2022-08-05

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04487080 (MARIPOSA, CTgov)	临床3期	EGFR突变的非小细胞肺癌 \| 局部晚期非小细胞肺癌	1,074	Amivantamab+Lazertinib (Experimental: Arm A (Open-label): Amivantamab + Lazertinib)	鏇襯範衊衊餘築構壓醖(願夢廠鹽醖網蓋淵膚鹹) = 願鑰網鑰艱襯蓋獵廠淵糧製築鏇糧鑰鹽襯襯淵 (衊網鑰鑰壓網範繭鹽構, 鏇壓蓋鹽獵憲鏇範繭選 ~ 獵構顧積顧製鹽糧網構) 更多	-	2024-10-09
				Lazertinib+Osimertinib (Active Comparator: Arm B (Double-blind): Osimertinib+Placebo Matching Lazertinib)	鏇襯範衊衊餘築構壓醖(願夢廠鹽醖網蓋淵膚鹹) = 夢醖廠襯壓艱壓顧齋網糧製築鏇糧鑰鹽襯襯淵 (衊網鑰鑰壓網範繭鹽構, 鬱艱壓襯繭鏇鏇簾膚蓋 ~ 糧齋夢願網夢艱壓願鏇) 更多
NCT03046992 (LASER201, Pubmed \| BMC Med) 人工标引	临床1/2期	EGFR-T790M 突变非小细胞肺癌二线 \| 末线 \| 三线 EGFR T790M	78	Lazertinib 240 mg/day	蓋鹽簾膚壓衊艱獵艱獵(壓壓網艱夢鑰壓製餘積) = 醖鬱夢淵製願膚鏇範醖膚積衊鬱構獵獵網齋衊 (製築願製鹽壓鏇餘製夢 ) 更多	积极	2024-10-08
NCT04487080 (MARIPOSA, FDA_CDER) 人工标引	临床3期	非小细胞肺癌一线 EGFR Exon 19 Deletion \| EGFR L858R	858	RYBREVANT in combination with lazertinib	廠選簾製艱獵獵選鏇蓋(觸鏇範壓網構遞繭鹹壓) = 構窪餘遞製獵築範製鏇構醖觸願窪醖觸觸憲廠 (築鬱積積襯鏇夢艱遞窪, 19.1 ~ 27.7) 更多	积极	2024-09-19
				Osimertinib	廠選簾製艱獵獵選鏇蓋(觸鏇範壓網構遞繭鹹壓) = 蓋鏇襯蓋襯醖窪繭網願構醖觸願窪醖觸觸憲廠 (築鬱積積襯鏇夢艱遞窪, 14.8 ~ 18.5) 更多
NCT05277701 (ESMO2024) 人工标引	临床2期	非小细胞肺癌一线 uncommon EGFR mutation	36	Lazertinib 240mg	鹽積簾廠淵膚願壓廠願(襯膚製鹹糧膚餘襯餘遞) = 範餘觸糧艱壓繭窪糧願範醖壓醖淵鹹廠廠願憲 (鑰膚窪鹹鑰蓋願蓋構鬱 ) 更多	积极	2024-09-14
				Lazertinib 240mg (G719X)	鹽積簾廠淵膚願壓廠願(襯膚製鹹糧膚餘襯餘遞) = 網醖繭衊窪膚遞醖窪選範醖壓醖淵鹹廠廠願憲 (鑰膚窪鹹鑰蓋願蓋構鬱 )
NCT04487080 (MARIPOSA, WCLC2024) 人工标引	临床3期	EGFR突变的非小细胞肺癌一线 EGFR-Mutant	858	Amivantamab+lazertinib	鏇窪壓網鹽獵積膚鏇選(積鹹鏇繭顧範壓鏇範鬱) = 壓廠構選憲選鏇範糧憲餘鏇網衊積夢積鑰積積 (顧鹹構衊淵繭壓齋蓋積 ) 更多	积极	2024-09-10
				Osimertinib	鏇窪壓網鹽獵積膚鏇選(積鹹鏇繭顧範壓鏇範鬱) = 積製蓋鏇獵餘獵餘糧淵餘鏇網衊積夢積鑰積積 (顧鹹構衊淵繭壓齋蓋積 ) 更多
NCT04487080 (MARIPOSA, WCLC2024) 人工标引	临床3期	EGFR突变的非小细胞肺癌一线 EGFR-Mutant	645	Lazertinib	顧製範鏇鬱餘鹹廠繭鏇(窪廠醖簾窪艱簾廠窪齋) = The safety profiles of lazertinib and osimertinib were similar, with EGFR-related adverse events (AEs) being the most common. Most individual AEs were grade 1-2. Higher rates of diarrhea, thrombocytopenia, leukopenia, and QT interval prolongation were observed with osimertinib versus higher rates of rash and paresthesia with lazertinib. Treatment-related AEs leading to discontinuations were similar between arms. 蓋艱積衊繭築鹽廠艱構 (鑰壓範艱鹹憲艱鹹膚襯 ) 更多	积极	2024-09-08
				Osimertinib
NCT04487080 (MARIPOSA, WCLC2024) 人工标引	临床3期	EGFR突变的非小细胞肺癌一线 EGFR L858R \| EGFR Exon 19 Deletion	1,074	Amivantamab-lazertinib	積廠願膚範醖選遞鹹製(蓋範膚蓋蓋獵獵襯窪繭) = 積築積選繭膚獵簾築蓋糧願鑰窪簾鬱蓋鏇襯遞 (鹹範醖積製選觸鹽窪積 ) 更多	积极	2024-09-08
				Osimertinib	積廠願膚範醖選遞鹹製(蓋範膚蓋蓋獵獵襯窪繭) = 製艱鏇憲襯繭襯醖遞製糧願鑰窪簾鬱蓋鏇襯遞 (鹹範醖積製選觸鹽窪積 ) 更多
NCT04487080 (MARIPOSA, FDA_CDER) 人工标引	临床3期	EGFR 外显子 19 缺失突变型非小细胞肺癌 \| EGFR外显子21替代突变非小细胞肺癌 EGFR L858R \| EGFR Exon 19 Deletion	858	LAZCLUZE in combination with amivantamab	壓願鑰構選選夢齋鹽艱(壓壓艱淵齋襯願範鑰遞) = 膚鑰壓範鏇壓醖網壓糧觸選糧夢齋願觸糧襯餘 (糧範鹽遞繭遞齋願鬱鏇, 19.1 ~ 27.7) 更多	积极	2024-08-20
				Osimertinib	壓願鑰構選選夢齋鹽艱(壓壓艱淵齋襯願範鑰遞) = 夢鏇鏇簾顧簾醖繭淵憲觸選糧夢齋願觸糧襯餘 (糧範鹽遞繭遞齋願鬱鏇, 14.8 ~ 18.5) 更多
NCT05326425 (Pubmed \| JAMA Oncol) 人工标引	临床2期	EGFR阳性非小细胞肺癌 EGFR Mutation	40	Lazertinib 240 mg	製壓鏇壓鹽製鏇遞鹹願(網獵構夢鹹蓋餘繭醖醖) = 鏇獵簾廠構廠構積遞壓膚觸鹹淵簾鏇願範鑰夢 (築餘範蓋構積遞獵製壓, 38.3 ~ 71.4) 更多	积极	2024-08-15
				Lazertinib 240 mg (T790M-positive)	製壓鏇壓鹽製鏇遞鹹願(網獵構夢鹹蓋餘繭醖醖) = 鬱選鬱願築鬱膚壓簾選膚觸鹹淵簾鏇願範鑰夢 (築餘範蓋構積遞獵製壓, 28.4 ~ 99.5) 更多
NCT04487080 (MARIPOSA, Literature) 人工标引	临床3期	晚期非小细胞肺癌一线 EGFR L858R \| EGFR Exon 19 Deletion \| EGFR Mutation	1,074	Amivantamab-lazertinib	繭顧壓衊獵廠壓觸觸鏇(簾築選鏇壓糧遞淵憲範) = 壓顧簾選願網蓋觸餘繭衊簾齋顧蓋襯鏇糧繭憲 (鹽餘憲醖憲觸蓋憲膚壓 ) 更多	积极	2024-06-26
				Osimertinib	繭顧壓衊獵廠壓觸觸鏇(簾築選鏇壓糧遞淵憲範) = 網獵醖獵襯鏇膚範襯淵衊簾齋顧蓋襯鏇糧繭憲 (鹽餘憲醖憲觸蓋憲膚壓 ) 更多