Study on the correlation between intestinal microbiota differential metabolites and the efficacy and gastrointestinal reactions of third-generation EGFR-TKI

开始日期2025-03-18

申办/合作机构-

NCT06441045

/ Not yet recruiting临床2期IIT

Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus Double Dose of Third-generation EGFR-TKI in NSCLC Patients With Leptomeningeal Progression Following the Treatment of Routine Dose of Third-generation EGFR-TKI: a Phase II Randomized, Multicenter Study

We aim to compare the efficacy and safety of double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus double Dose of Third-generation EGFR-TKI in patients with leptomeningeal progression following the treatment of routine dose of EGFR-TKI,

开始日期2024-10-01

申办/合作机构

福建省肿瘤医院（福建省肿瘤研究所、福建省癌症防治中心）

JPRN-UMIN000054805

/ SuspendedN/AIIT

Phase Ia/Ib Basket Trial on the safety and efficacy of Mobocertinib in combination with T-DM1 for patients with HER2 mutant solid tumors Biomarker study (WJOG16022MTR) - WJOG16022MTR

开始日期2024-07-22

申办/合作机构-

100 项与琥珀酸莫博赛替尼相关的临床结果

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100 项与琥珀酸莫博赛替尼相关的转化医学

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100 项与琥珀酸莫博赛替尼相关的专利（医药）

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2,927

项与琥珀酸莫博赛替尼相关的文献（医药）

2025-12-01·CANCER CHEMOTHERAPY AND PHARMACOLOGY

Pharmacokinetics, mass balance, and metabolism of [14C]PLB1004, a selective and irreversible EGFR-TKI in humans

Article

作者: Geng, Fei ; Yan, Shu ; Zhang, Peilong ; Zhao, Furong ; Wang, Feiyu ; Xue, Weizhe ; Gao, Lei ; Ye, Panpan ; Liu, Donghui ; Li, Weiqiang ; Diao, Xingxing ; Zhao, Wei ; Li, Qian ; Zhang, Xinyue ; Zhou, Haiyan

PURPOSE:

PLB1004, developed by Beijing Avistone Biotechnology Co., Ltd., is a safe, highly selective, and efficient irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) employed in treating non-small-cell-lung-cancer (NSCLC). This study investigated its pharmacokinetics, mass balance, and metabolism in 6 healthy Chinese male subjects treated with 160 mg (70 µCi) [¹⁴C]PLB1004.

METHODS:

Following drug administration, samples of blood, urine and feces were collected for quantitative determination of total radioactivity and metabolites were identified through radioactivity detection coupled with UHPLC-MS/MS.

RESULTS:

Following drug administration, the median radioactive T_max was 4.17 h in plasma, with the average t_1/2 of PLB1004-related components in plasma of approximately 54.3 h. Over 264 h post-administration, the average cumulative excretion among the six subjects was 95.01% of the administered dose, with 84.71% and 10.30% excreted in feces and urine, respectively. Nine metabolites were characterized and identified and the parent drug PLB1004 was detected in plasma, urine, and feces. Among these metabolites, M689 was the most prevalent one in plasma, urine, and feces, constituting 25.37% of the total plasma radioactivity, and 55.88% and 1.73% of the administrated dose in feces and urine, respectively.

CONCLUSION:

Fecal excretion emerged as PLB1004 excretion route, while urinary excretion via the kidneys served as the secondary route. The primarily metabolic pathways are oxidation, demethylation, dehydrogenation, and cysteine conjugation in humans.

2025-04-01·Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners

Correlation analysis of EGFR gene mutation abundance and the efficacy of targeted therapy with osimertinib in nonsmall cell lung cancer—a case control study

Article

作者: He, Changjin ; Peng, Jigui ; Chen, Hui ; Yan, Haiqiang ; Zhou, Wang

Background:

In nonsmall cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutation is the primary cancer-causing mutation. But whether the practical effectiveness of EGFR tyrosine kinase inhibitors (TKIs) can be influenced by plasma EGFR mutation abundance when treating patients with advanced NSCLC remains unanswered. Therefore, this research was intended to reveal the connection between plasma EGFR mutation abundance and clinical outcomes in osimertinib-treated patients with advanced NSCLC.

Methods:

A total of 120 patients with advanced NSCLC were retrospectively analyzed, and 56 patients with EGFR-mutation-positive NSCLC receiving osimertinib first-line therapy were eventually screened and included. The baseline status and abundance of plasma EGFR in patients with NSCLC were detected by cSMART, and the ratio of 0.1 was the critical value. Imaging examinations were performed every 8–12 weeks for the assessment of tumor response. The relationship between baseline EGFR mutation abundance and clinical outcomes of TKI therapy was analyzed.

Results:

The objective response rates (ORR) of EGFR-mutant patients in the high-/low-abundance groups were 69.2% and 40.0%, respectively. The high abundance group had an obviously higher ORR than the low abundance group ( P = 0.029). A much longer median progression-free survival (mPFS) was demonstrated in patients with high mutation abundance than in patients with low abundance (11.2 months vs 7.1 months, P = 0.0133). As for the median overall survival (mOS), it showed the same trend as mPFS in patients from different groups (15.5 vs 10.7 months, P = 0.0028). The role of plasma mutation abundance as an independent prognostic factor for both PFS (hazard ratios [HR]: 0.30, P = 0.006) and OS (HR: 0.35, P = 0.004) was demonstrated by multivariate Cox regression analysis.

Conclusion:

There is a close connection between plasma EGFR mutation abundance and survival benefit in patients with NSCLC, which can be used for predicting the efficacy of EGFR-TKI targeted therapy. Our study is expected to provide a research basis for screening patients to whom the EGFR-TKI therapy is beneficial.

2025-04-01·INTERNATIONAL JOURNAL OF CANCER

Prognostic impact of PD‐L1 expression in surgically resected EGFR‐mutant lung adenocarcinoma: A real‐world database study in Japan (CReGYT‐01 EGFR study)

Article

作者: Tsuboi, Masahiro ; Suda, Kenichi ; Shien, Kazuhiko ; Shiono, Satoshi ; Soh, Junichi ; Muto, Satoshi ; Katsumata, Shinya ; Matsubara, Taichi ; Suzawa, Ken ; Nomura, Kotaro ; Fujino, Kosuke ; Hamada, Akira ; Aokage, Keiju ; Kinoshita, Fumihiko ; Okamoto, Tatsuro ; Haratake, Naoki ; Ohde, Yasuhisa ; Fukuda, Shota ; Shimokawa, Mototsugu ; Hirai, Fumihiko ; Ohara, Shuta ; Suzuki, Hiroyuki ; Takada, Kazuki ; Kouki, Yasunobu ; Yoshikawa, Mao

Abstract:

The expression of programmed cell death‐ligand 1 (PD‐L1) and mutation in epidermal growth factor receptor (EGFR) are biomarkers used for perioperative treatment of lung adenocarcinoma. However, the clinical significance of PD‐L1 expression in surgically resected EGFR‐mutant lung adenocarcinoma remains unclear. We conducted a real‐world database of patients with surgically resected lung adenocarcinoma from 2015 to 2018 was constructed across 21 centers in Japan. The association among PD‐L1 expression, EGFR mutations, and prognosis was evaluated. Among 847 patients, PD‐L1 expression was negative (tumor proportion score [TPS] < 1%) in 429 (51%), weakly positive (TPS = 1%–49%) in 275 (32%), and strongly positive (TPS ≥50%) in 143 (17%) patients. EGFR mutations were detected in 331 (39%) patients. PD‐L1 expression was associated with poor recurrence‐free survival (RFS) (p < .001) in both EGFR‐mutant and wild‐type patients. However, in EGFR‐mutant patients, PD‐L1 expression was not associated with overall survival (OS) (p = .506). Multivariable analysis confirmed an association between PD‐L1 expression and RFS but not OS. Furthermore, in EGFR‐mutant patients treated with EGFR‐tyrosine kinase inhibitor (EGFR‐TKI) treatment post‐relapse, PD‐L1 expression was not associated with overall response rate (p = .714), disease control rate (p = .554), or progression‐free survival (p = .660). In conclusion, PD‐L1 expression predicted poor RFS‐independent EGFR status but did not show any association with OS in EGFR‐mutant patients. The efficacy of post‐relapse EGFR‐TKI treatment was independent of PD‐L1 expression. The significance of PD‐L1 expression in perioperative EGFR‐TKI therapy should be evaluated.

1,505

项与琥珀酸莫博赛替尼相关的新闻（医药）

2025-03-22

·肿瘤界

Nature Medicine | 吴一龙教授揭示非小细胞肺癌患者术后监测MRD的临床价值

点击蓝字关注我们 2025年3月17日，广东省人民医院吴一龙教授、美国耶鲁大学Roy S. Herbst共同通讯在Nature Medicine（IF=58.7）在线发表题为“Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer”的研究论文，该研究报告了EGFR突变IB–IIIA期非小细胞肺癌（NSCLC）切除后奥希替尼辅助治疗的分子残留病（MRD）分析结果。结果表明术后MRD检测或可预测辅助治疗期间及停药后的疾病复发，以及识别潜在受益于奥希替尼长期辅助治疗的患者。奥希替尼（Osimertinib）是第三代EGFR-TKI，在早期和晚期EGFR突变（Ex19del/L858R）NSCLC中显示出疗效。根据3期ADAURA试验结果，推荐IB-IIIA期EGFR突变NSCLC患者术后接受3年奥希替尼辅助治疗。ADAURA初步分析显示，无论是否接受过化疗，奥希替尼辅助治疗较安慰剂显著（统计学/临床意义）改善IB-IIIA期EGFR突变NSCLC完全切除术后的DFS。延长2年随访的更新分析中，DFS获益持续存在，并转化为总生存率（OS）的显著改善：奥希替尼组5年OS率为88%，安慰剂组为78%，死亡HR=0.49（95.03%CI: 0.34-0.70，P<0.001）。完成3年奥希替尼治疗后DFS率有上升趋势，提示延长奥希替尼治疗时间或可进一步改善部分患者结局，但如何筛选此类患者仍不明确。根治性治疗后的标准监测模式包括连续影像学检查，但该方法仅能检测宏观病灶，且易受治疗后正常组织变化干扰，并且监测的最佳扫描频率也不确定。循环肿瘤DNA（ctDNA）可通过液体活检（如血浆）检测到，是评估肿瘤负荷和基因组改变的一种微创诊断工具。MRD（即根治性治疗后监测ctDNA）或可作为早期复发的生物标志物，具有指导治疗和预后的潜力。由于患者疾病早期肿瘤负荷低且ctDNA比例低，因此ctDNA的检测可能具有挑战性。第二代测序（NGS）技术的进步提高了ctDNA检测灵敏度，使得基于肿瘤分子特征的个性化MRD检测更具可行性。该技术利用患者肿瘤基因组谱，纵向追踪血浆ctDNA中的个体化肿瘤特异性改变。几项针对接受根治性治疗的早期NSCLC患者的研究支持使用基于肿瘤分子特征的MRD检测预测影像学复发。针对I-III期NSCLC患者的研究，例如一项纳入261例患者的前瞻性研究和一项纳入88例患者的LUCID研究显示，MRD检测较影像学识别疾病进展分别提前中位3.4个月和212.5天（约7个月）。在一项纳入40例I-III期NSCLC患者（接受放疗、化疗和/或手术）的回顾性分析中，72%患者的ctDNA检测较影像学识别疾病进展提前中位5.2个月。尽管研究有限，但这些数据提示基于肿瘤分子特征的MRD检测在早期NSCLC中的潜在应用价值。本研究对ADAURA试验中的220例患者（奥希替尼组n=112；安慰剂组n=108）进行探索性分析，探讨基于血浆与肿瘤分子特征的MRD检测能否预测辅助治疗期间及停药后的疾病复发，并探究治疗前肿瘤基因组改变与分子及临床结局的关联。本文报道了一项EGFR突变NSCLC患者术后长期纵向MRD分析结果的3期随机临床试验。 MRD分析集中患者血浆样本的纵向MRD分析本研究中，MRD检测较影像学检测复发的中位提前时间为4.7个月（95%CI：2.2-5.6）。36个月时，奥希替尼组与安慰剂组MRD阴性的DFS率分别为86% vs 36%（HR=0.23，95%CI: 0.15-0.36）。奥希替尼组中，28例（25%）患者检测到复发或MRD阳性；其中68%（19/28）发生于停药后，58%（11/19）发生于停药后12个月内。停药24个月后MRD阴性DFS率为66%。两组中多数患者检测到MRD阳性早于复发。辅助治疗期间及治疗后随访中，大部分患者维持DFS和MRD阴性，多数MRD阳性或复发发生于停药或完成治疗后。研究结果显示，MRD检测或可识别从延长奥希替尼辅助治疗中获益的患者，但需临床验证。综上所述，这项针对ADAURA试验患者的探索性分析表明，基于血浆及肿瘤分子特征MRD分析或可预测辅助治疗期间及停药后的疾病复发。研究还发现，大多数患者在奥希替尼辅助治疗期间及停药后24个月内维持无复发。这些观察结果提示，MRD监测或可指导临床干预（如重启或强化治疗）。但在将其常规应用于真实临床实践前，需开展前瞻性研究以明确辅助治疗完成后MRD监测的最佳频率及检测到MRD阳性后的适宜临床干预措施。推荐阅读 ● Nature Medicine | 吴一龙教授团队揭示脑脊液ctDNA于CNS转移瘤的重要临床价值 ● JCO丨吴一龙团队发表Vebreltinib治疗c-MET外显子14跳跃突变型非小细胞肺癌研究结果 ● 吴一龙团队新成果荣登《JAMA Oncology》首创晚期肺癌药物假期模式 ● NEJM | 吴一龙领衔全球研究，有望改写ALK阳性非小细胞肺癌辅助治疗声明：本文由“肿瘤界”整理与汇编，欢迎分享转载，如需使用本文内容，请务必注明出处。编辑：lagertha 审核：松月、南星

临床3期临床结果信使RNA

2025-03-21

·康方生物

SGO 2025丨康方生物卡度尼利联合同步放化疗治疗局部晚期宫颈癌疗效优异

近日，康方生物（9926.HK）在2025年美国妇科肿瘤学会（SGO）年会上发布了其独立自主研发的全球首创PD-1/CTLA-4双特异性抗体卡度尼利（AK104）联合同步放化疗（CCRT）治疗局部晚期宫颈癌的Ⅲ期临床研究COMPASSION-18/AK104-305的安全性导入阶段优异数据。这一重要进展不仅再次证明了卡度尼利在更广泛宫颈癌患者群体中的治疗价值，更彰显了其在宫颈癌治疗领域的卓越疗效和广阔应用前景。作为局部晚期宫颈癌的标准治疗方案，CCRT仍面临30%-40%患者在5年内复发或进展的治疗困境。卡度尼利具有独特的双靶点机制，能够同时阻断PD-1和CTLA-4免疫检查点通路，在宫颈癌治疗中已经展现出巨大的临床价值。目前，卡度尼利已获得中国国家药品监督管理局（NMPA）批准用于既往接受含铂化疗治疗失败的复发或转移性宫颈癌患者。III 期临床研究COMPASSION-16研究也已证实，卡度尼利联合含铂化疗（无论是否联合贝伐珠单抗）可显著延长一线持续性、复发性或转移性宫颈癌患者的无进展生存期（PFS）和总生存期（OS）。基于这一显著疗效，卡度尼利方案一线治疗持续、复发或转移性宫颈癌的新药上市申请（sNDA）已处于审评审批阶段。在本届SGO报道了COMPASSION-18研究中，在安全性导入阶段接受卡度尼利联合CCRT治疗的患者展现出的卓越的疗效，展示了卡度尼利联合CCRT在局部晚期宫颈癌中的巨大的治疗潜力。研究纳入了更具挑战性的患者群体，其中PD-L1 CPS＜1（38.2%）和ECOG评分为1（52.9%）的患者比例显著高于同类研究。可评估患者的最佳总缓解率（ORR）达到100%，其中完全缓解（CR）率高达84.8%，部分缓解（PR）率为15.2%，远优于同类型研究数据；中位缓解持续时间（DoR）尚未达到。无进展生存期（PFS）未达到，12个月无进展生存率达74.9%。亚组分析显示，PD-L1 CPS≥1、ECOG评分为0、未感染COVID-19的患者从该治疗方案中的获益趋势更明显，12个月PFS率分别为85%、87.5%和81.3%。卡度尼利联合CCRT展现出良好的耐受性，临床安全可控，未出现因TRAE导致的死亡事件，未出现新的安全性信号。从复发/转移性宫颈癌到局部晚期宫颈癌，卡度尼利在宫颈癌治疗领域的突破性成果不断涌现。COMPASSION-18研究的积极数据进一步验证了卡度尼利在更广泛患者群体中的治疗潜力。随着临床开发的深入推进，卡度尼利正在逐渐重塑宫颈癌治疗格局，为更多患者带来长期生存获益。说明：本文作为康方生物的新闻发布，用于披露公司最新进展，并非产品推广广告，不构成康方生物的信息披露或投资建议。关于开坦尼®（卡度尼利单抗注射液）开坦尼®是康方生物自主研发的全球首创PD-1/CTLA-4双特异性肿瘤免疫治疗药物，2022年6月获得国家药品监督管理局的批准，用于既往接受含铂化疗治疗失败的复发或转移性宫颈癌患者的治疗。2024年9月，开坦尼®联合方案用于局部晚期不可切除或转移性胃或胃食管结合部（G/GEJ）腺癌患者一线治疗适应症获批上市。开坦尼®加含铂化疗联合/不联合贝伐珠单抗一线治疗持续、复发或转移性宫颈癌的新药上市申请正在审评审批阶段。开坦尼®是世界上第一个肿瘤免疫治疗双抗新药，也是中国的第一个双特异性抗体新药。开坦尼®既往接受含铂化疗失败的复发或转移性宫颈癌适应症于2024年11月被纳入2024年国家医保目录。开坦尼®已针对胃癌、肺癌、肝癌、宫颈癌、胰腺癌等16种恶性肿瘤疾病开展了23项以上的临床研究。开坦尼®是一种全新机制的肿瘤免疫治疗药物，可以同时靶向PD-1和CTLA-4发挥协同抗肿瘤的作用，具有优异的抗肿瘤疗效，相比联合疗法的毒性显著降低，安全可耐受。多项临床研究显示，开坦尼®针对多种肿瘤疾病的PD-L1表达阳性和阴性患者均具有优异的抗肿瘤疗效，临床差异化价值凸显。目前，开坦尼®已被16项临床治疗指南和共识重磅推荐，覆盖胃癌、妇科肿瘤、肝癌、食管癌、鼻咽癌等多个适应症。关于康方生物康方生物（9926.HK）是一家集研究、开发、生产及商业化全球首创或同类最佳创新生物新药于一体的领先企业。自2012年成立以来，公司始终以患者为中心，以临床价值为导向，打造了独有的端对端康方全方位新药研究开发平台，建立了以Tetrabody双特异性抗体开发技术、抗体偶联（ADC）技术、mRNA技术及细胞治疗技术为核心的研发创新体系，国际化标准的GMP生产体系和运作模式先进的商业化体系，成为了在全球范围内具有竞争力的生物医药创新公司。公司已开发了50个以上用于治疗肿瘤、自身免疫、炎症、代谢疾病等重大疾病的创新候选药物，23个候选药已进入临床（包括11个双抗/多抗/双抗ADC），6个新药已在商业化销售，5个新药多个适应症的上市申请处于审评审批阶段。康方生物是全球迄今唯一拥有2个肿瘤免疫双抗新药的制药公司：2022年6月，公司全球首创的PD-1/CTLA-4双抗开坦尼®获批上市，是全球首个获批的肿瘤免疫治疗双抗新药，也是中国第一个双特异性抗体新药。目前开坦尼®一线治疗胃癌和治疗复发/转移性宫颈癌适应症已获批，一线治疗宫颈癌sNDA已受理，另有8个注册III期临床开展中。2024年5月，公司另一全球首创双抗新药依达方®获批上市，用于EGFR-TKI治疗进展的局部晚期或转移性nsq-NSCLC，是全球首个获批的“肿瘤免疫+抗血管生成”机制双抗新药。同期，依达方®在与全球“药王”帕博利珠单抗的随机、双盲、对照一线治疗PD-L1阳性NSCLC的“头对头”III期临床研究中获得显著阳性结果，依达方®可降低患者疾病进展/死亡风险达49%，依沃西成为全球迄今唯一在头对头III期临床研究中证明疗效显著优于“药王”帕博利珠单抗的药物。基于该研究结果，依沃西同适应症的sNDA获CDE受理，并获优先审评，将有望成为一线肺癌治疗新的标准治疗方案，为患者提供全新更优的“去化疗”选择。目前依达方®有11项注册性III期临床正在开展，包括3项国际多中心注册性III期临床研究。2024年12月，开坦尼®、依达方®均通过医保谈判被纳入国家新版医保目录。国际市场开发是康方生物核心发展战略，继2015年开中国先河将自主研发的CTLA-4单抗权益许可给默沙东公司之后，2022年12月，公司再次创造中国记录，以50亿美金+2位数百分比销售提成的方案，将依达方®部分海外权益许可给美国Summit公司，该合作创下了彼时中国新药对外许可的最高交易金额记录。2025年2月，Summit 与美国辉瑞（Pfizer）公司达成临床试验合作，共同推进依达方®联合辉瑞多款抗体偶联药物（ADCs）在多种实体瘤中的联合治疗疗法。2024年9月，公司自主研发的伊喜宁®（伊努西单抗，PCSK9）治疗高胆固醇血症两项适应症获批，成为非肿瘤领域的首个获批产品。康方生物期望通过高效及突破性的研发创新，开发国际首创及同类药物最佳疗法的新药，为全球患者提供更优疾病解决方案，成为全球领先的生物制药企业。

临床3期临床结果

2025-03-20

·PRNewswire

Dizal's Golidocitinib in Combination with Anti-PD-1 Shows Promise in IO Resistant Non-Small Cell Lung Cancer

Golidocitinib is a JAK1 only inhibitor approved for the treatment of relapsed or refractory PTCL The combination of golidocitinib and PD-1 antibody showed synergistic anti-tumor effects in anti-PD-1-resistant NSCLC SHANGHAI, March 20, 2025 /PRNewswire/ -- Dizal (SSE: 688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, today announced new findings on golidocitinib, a first-in-class Janus kinase 1 (JAK1) only inhibitor, in combination with PD-1 antibodies for patients who have progressed on anti-PD-1 therapy. The details of the trial design and clinical results will be presented at the 2025 European Lung Cancer Congress (ELCC 2025) in Paris, March 26-29. Recent studies showed that the dysregulated activation of the JAK/STAT pathway, which leads to the prolonged release of IFN-γ, is a significant contributor to the resistance to immune checkpoint inhibitors in cancer immunotherapy. Preclinical and clinical studies have demonstrated that the combination of JAK inhibitors with PD-1 immunotherapy can reverse or delay onset of immunotherapy resistance by modulating the JAK/STAT pathway in Hodgkin's lymphoma and NSCLC. Golidocitinib has shown excellent clinical benefits by effectively inhibiting the JAK/STAT pathway, leading to its approval for the treatment of relapsed/refractory peripheral T-cell lymphoma (r/r PTCL) in China. Preclinical studies also show that the combination of Golidocitinib and PD-1 antibody has synergistic potentials for anti-tumor effects. Building on these findings, an exploratory phase Ib clinical study combining golidocitinib with PD-1 antibodies was designed to explore the synergistic effects of this combined regimen in NSCLC patients who have failed from anti-PD-1 containing regimens. This study will enroll 30 locally advanced or metastatic NSCLC patients who have previously received anti-PD-1 monotherapy or anti-PD-1 therapy with platinum-containing chemotherapy regimens. "Immunotherapy alone or with chemotherapy is commonly used as front line treatment for NSCLC patients without driver mutations. Unfortunately, resistance is inevitable and once the disease progresses, the prognosis is poor and treatment option is limited." said Xiaolin Zhang, PhD, CEO of Dizal. "The findings we are presenting at ELCC 2025 highlight the potential for Golidocitinib-based combination regimen to delay or overcome the resistance. The preliminary results are very promising and justify further clinical validation." In addition to the golidocitinib-based combination therapy, positive results from a Phase II study of sunvozertinib in combination with Anlotinib will also be presented. Sunvozertinib combined with anlotinib was well tolerated and demonstrated encouraging antitumor activity in NSCLC patients with EGFR mutations who had failed prior EGFR-TKI therapies. As of December 25, 2024, the objective response rate (ORR) and the disease control rate (DCR) were 33.3% and 100%, respectively, in this heavily pre-treated patient population. Enrollment is ongoing and detailed results will be updated at the congress. Dizal presentation details during ELCC 2025 About golidocitinib (DZD4205) Golidocitinib is currently the first and only Janus kinase 1 (JAK1) selective inhibitor being evaluated for the treatment of r/r PTCL. In June 2024, golidocitinib was approved by the National Medical Products Administration (NMPA) of China for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (r/r PTCL). At the data cut-off date of August 31, 2023, golidocitinib has demonstrated robust and durable anti-tumor efficacy, with an ORR of 44.3%. More than 50% of the patients with tumor remission achieved a complete response with a CRR of 23.9%. Per IRC assessment, mDoR reached 20.7 months. Golidocitinib was granted Fast Track Designation by the U.S. FDA for the treatment of r/r PTCL in February 2022. In September 2023, the CDE accepted its NDA and granted Priority Review for the treatment of r/r PTCL. The Phase I clinical data of golidocitinib (JACKPOT8 PART A) was published in Annals of Oncology (Impact Factor: 51.8), and global pivotal trial data of golidocitinib for the treatment of r/r PTCL (JACKPOT PART B) was published in The Lancet Oncology (Impact Factor: 54.4). About sunvozertinib (DZD9008) Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M, and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins. Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable. Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins. Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery and The Lancet Respiratory Medicine. About Dizal Dizal is a biopharmaceutical company, dedicated to the discovery, development, and commercialization of differentiated therapeutics for the treatment of cancer and immunological diseases. The company aims to develop first-in-class and groundbreaking new medicines, and further address unmet medical needs worldwide. Deep-rooted in translational science and molecular design, it has established an internationally competitive portfolio with two approved drugs and multiple assets in global pivotal studies. To learn more about Dizal, please visit , or follow us on Linkedin or Twitter. Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", and "intend" and similar expressions, as they relate to Dizal, are intended to identify certain forward-looking statements. Dizal does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections, and understandings of the management of Dizal with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties, and other factors, some of which are beyond Dizal's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Dizal's competitive environment, and political, economic, legal, and social conditions. Dizal, the Directors, and the employees of Dizal assume (a) no obligation to correct or update the forward-looking statements contained on this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turnout to be incorrect. Contacts Investor Relations: [email protected] Business Development: [email protected] Media Contact: [email protected] SOURCE Dizal Pharmaceutical WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果免疫疗法临床1期快速通道上市批准

100 项与琥珀酸莫博赛替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11969	-	-	-

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 20号外显子插入突变非小细胞肺癌	美国	Takeda Pharmaceuticals U.S.A., Inc.	2021-09-15

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
转移性非小细胞肺癌	临床2期	-	Takeda Pharmaceutical Co., Ltd.	2020-11-30
局部晚期非小细胞肺癌	临床2期	美国	Takeda Pharmaceutical Co., Ltd.	2016-06-16
局部晚期非小细胞肺癌	临床2期	中国	Takeda Pharmaceutical Co., Ltd.	2016-06-16
局部晚期非小细胞肺癌	临床2期	日本	Takeda Pharmaceutical Co., Ltd.	2016-06-16
局部晚期非小细胞肺癌	临床2期	德国	Takeda Pharmaceutical Co., Ltd.	2016-06-16
局部晚期非小细胞肺癌	临床2期	意大利	Takeda Pharmaceutical Co., Ltd.	2016-06-16
局部晚期非小细胞肺癌	临床2期	波多黎各	Takeda Pharmaceutical Co., Ltd.	2016-06-16
局部晚期非小细胞肺癌	临床2期	西班牙	Takeda Pharmaceutical Co., Ltd.	2016-06-16
局部晚期非小细胞肺癌	临床2期	中国台湾	Takeda Pharmaceutical Co., Ltd.	2016-06-16
局部晚期非小细胞肺癌	临床2期	英国	Takeda Pharmaceutical Co., Ltd.	2016-06-16

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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


NCT04129502 (EXCLAIM-2, Pubmed \| J Clin Oncol) 人工标引	临床3期	EGFR 20号外显子插入突变非小细胞肺癌一线 EGFR exon 20 insertion	354	Mobocertinib 160 mg	衊鬱顧餘鏇願鑰構範鹽(膚構網構艱積醖窪觸遞) = 製網製構憲鏇築鬱衊獵衊蓋網壓憲觸廠艱艱願 (獵顧範觸選齋蓋繭廠範 ) 未达到更多	不佳	2025-01-29
				Pemetrexed plus cisplatin or carboplatin	衊鬱顧餘鏇願鑰構範鹽(膚構網構艱積醖窪觸遞) = 壓選夢選廠齋衊繭廠鑰衊蓋網壓憲觸廠艱艱願 (獵顧範觸選齋蓋繭廠範 ) 未达到更多
WCLC2024	N/A	非小细胞肺癌	-	Osimertinib	願積積選遞蓋夢蓋憲簾(鏇齋窪餘鬱積窪獵鬱構) = 選夢膚獵鹽餘鬱鹽鏇醖膚鹽淵糧膚選網繭夢醖 (遞糧構齋窪淵夢鹹鹽網 ) 更多	-	2024-09-07
				Furmonertinib	願積積選遞蓋夢蓋憲簾(鏇齋窪餘鬱積窪獵鬱構) = 糧獵壓窪選鏇繭簾窪餘膚鹽淵糧膚選網繭夢醖 (遞糧構齋窪淵夢鹹鹽網 ) 更多
JPRN-jRCT2051220070 (WJOG16022M, ASCO2024)	临床1期	实体瘤 HER2 mutations	28	Mobocertinib 80 mg	艱顧簾夢網窪積網鹽艱(製夢鬱製遞鏇獵醖醖醖) = grade ≥ 3 AE occurred in 72.7% of pts; the common events (>5%) being thrombocytopenia (50.0%), diarrhea (13.6%), and anorexia (13.6%) 夢壓淵壓範顧鹹選醖鑰 (鏇襯壓夢範鏇觸糧鏇壓 )	积极	2024-05-24
NCT03811834 (phase 1 study, Pubmed)	临床1期	EGFR exon 20 insertion mutations	-	Mobocertinib 160 mg	廠繭觸築淵鏇製築糧鑰(醖膚廠獵夢蓋夢窪窪鹹) = all adverse events were Grade 1 in severity 選憲顧鑰糧網獵構襯築 (鹽選網遞齋築鬱構積餘 )	-	2024-05-24
				[14C]-Mobocertinib 50 µg
NCT04051827 (CTgov)	临床1期	晚期非小细胞肺癌	26	Midazolam (Part A: Midazolam Alone)	選簾選鹹遞範範築繭鬱(網構選淵顧鑰選觸淵鏇) = 衊顧顧鏇選淵築襯糧憲簾壓鹽鹹獵夢齋襯鏇醖 (築蓋範蓋窪鬱襯淵糧壓, 60.2) 更多	-	2024-04-12
				Midazolam+Mobocertinib (Part A: Midazolam + Mobocertinib)	選簾選鹹遞範範築繭鬱(網構選淵顧鑰選觸淵鏇) = 積鹽積醖積選範獵鑰憲簾壓鹽鹹獵夢齋襯鏇醖 (築蓋範蓋窪鬱襯淵糧壓, 60.7) 更多
NCT04056455 (CTgov)	临床1期	肿瘤	26	Mobocertinib (Severe Renal Impairment: Mobocertinib 80 mg)	醖簾繭鹽範窪夢艱構醖(積範鬱齋獵獵繭衊醖積) = 淵鑰膚膚窪襯衊壓衊構築壓夢憲簾願餘鏇觸艱 (夢顧顧壓膚鹽齋獵鏇齋, 326) 更多	-	2024-01-08
				Mobocertinib (Normal Renal Function: Mobocertinib 80 mg)	醖簾繭鹽範窪夢艱構醖(積範鬱齋獵獵繭衊醖積) = 簾顧獵願夢範願鹹醖鹽築壓夢憲簾願餘鏇觸艱 (夢顧顧壓膚鹽齋獵鏇齋, 69.8) 更多
NCT02716116 (ESMO_ASIA2023)	临床1/2期	非小细胞肺癌 EGFR ex20ins-positive	57	mobocertinib	鑰膚遞醖鹽廠鏇範襯選(鹽觸廠艱顧範構獵願糧) = 範積憲鑰餘鬱鹹遞築廠鬱衊鏇網鏇鬱窪獵壓遞 (膚願憲鹽廠構糧鏇淵範 ) 更多	-	2023-12-02
NCT04129502 (EXCLAIM-2, ESMO_ASIA2023)	临床3期	EGFR外显子20阳性肿瘤一线 EGFR ex20ins+	354	Mobocertinib 160 mg PO daily	蓋觸積壓獵膚鏇衊範繭(觸衊夢鏇鑰鹹網範蓋遞) = 夢鹽選鬱鹹淵願鹽鹹鬱夢願鏇窪鹽鹹廠積構憲 (壓鹽齋鹹廠簾廠觸觸遞 ) 更多	不佳	2023-12-02
				Pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2/carboplatin AUC 5 IV every 3 weeks for 4 cycles followed by maintenance pemetrexed	蓋觸積壓獵膚鏇衊範繭(觸衊夢鏇鑰鹹網範蓋遞) = 夢範憲蓋積衊鹽顧膚鏇夢願鏇窪鹽鹹廠積構憲 (壓鹽齋鹹廠簾廠觸觸遞 ) 更多
ESMO_ASIA2023	N/A	EGFR突变的非小细胞肺癌 EGFR exon 20 insertion mutations	105	Mobocertinib	構壓觸襯蓋簾願糧鬱顧(鹽構遞鏇鏇糧製選繭淵) = 51 patients (48.6%) reported diarrhea (all grades) related to mobocertinib (treatment discontinuation due to diarrhea: 4 patients [7.8%]) 膚構醖網鹹膚鏇簾範艱 (齋艱夢廠範選鬱繭鹹製 )	积极	2023-12-02
NCT04056468 (CTgov)	临床1期	肝损伤	24	Mobocertinib (Moderate HI (Child-Pugh B): Mobocertinib 40 mg)	選鏇繭鑰醖鬱糧窪簾膚(製觸構積築鹹獵積膚醖) = 獵淵築餘鑰鹽願鑰鬱膚顧遞襯夢壓遞簾願願廠 (蓋顧範壓壓遞齋網膚遞, 58.2) 更多	-	2023-11-03
				Mobocertinib (Severe HI (Child-Pugh C): Mobocertinib 40 mg)	選鏇繭鑰醖鬱糧窪簾膚(製觸構積築鹹獵積膚醖) = 顧製膚遞獵壓憲簾艱壓顧遞襯夢壓遞簾願願廠 (蓋顧範壓壓遞齋網膚遞, 31.7) 更多