1.主要目的：以山东朗诺制药有限公司生产的达可替尼片为受试制剂（T），以Pfizer Europe MA EEIG持证，Pfizer Manufacturing Deutschland GmbH生产的达可替尼片（商品名：VIZIMPRO®）为参比制剂（R），评估健康受试者在空腹和餐后状态下单次给药受试制剂和参比制剂的药代动力学特征。 2. 次要目的：考察健康受试者给药受试制剂和参比制剂后的安全性。

开始日期2023-12-30

申办/合作机构

山东朗诺制药有限公司

CTR20231341 / CompletedN/A

中国健康成年受试者在空腹/餐后状态下单次口服达可替尼片（45 mg）受试制剂和达可替尼片（45 mg）参比制剂（VIZIMPRO®）的生物等效性试验

主要研究目的：本研究以昆山龙灯瑞迪制药有限公司研制的达可替尼片（规格：45 mg）为受试制剂，按生物等效性研究的有关规定，以Pfizer Europe MA EEIG持证的欧盟上市的未进口原研药品达可替尼片（规格：45 mg，商品名：VIZIMPRO®）为参比制剂，评估受试制剂和参比制剂在空腹/餐后条件下给药后的生物等效性。次要目的：观察受试制剂达可替尼片和参比制剂达可替尼片（VIZIMPRO®）在健康受试者中的安全性。

开始日期2023-05-30

申办/合作机构

昆山龙灯瑞迪制药有限公司

CTR20230688 / CompletedN/A

达可替尼片在健康受试者中的单剂量、空腹和餐后、随机、开放、两周期、两交叉生物等效性研究

主要目的：评价中国健康成人受试者空腹/餐后状态下口服重庆药友制药有限责任公司生产的达可替尼片（15mg）与参比制剂达可替尼片（15mg，商品名：Vizimpro®）是否具有生物等效性。次要目的：评价受试制剂与参比制剂在健康受试者中的安全性。

开始日期2023-03-24

申办/合作机构

重庆药友制药有限责任公司

100 项与 EGFR外显子21替代突变非小细胞肺癌相关的临床结果

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100 项与 EGFR外显子21替代突变非小细胞肺癌相关的转化医学

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0 项与 EGFR外显子21替代突变非小细胞肺癌相关的专利（医药）

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项与 EGFR外显子21替代突变非小细胞肺癌相关的文献（医药）

2024-07-18·Cureus

Investigation of the Efficacy of Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor in Patients With EGFR Exon 21 L858R Point Mutation-Positive Non-small Cell Lung Cancer

Article

作者: Yamamura, Kouichi ; Ishige, Yoko ; Tanaka, Takuya ; Nojiri, Masafumi ; Iguchi, Masaharu ; Shionoya, Ikuyo ; Takahara, Yutaka ; Nagae, Sumito ; Abe, Ryudai

BACKGROUNDTreatment of advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has a higher response rate than with conventional chemotherapy in patients positive for EGFR mutations. However, the efficacy of EGFR-TKI therapy may be reduced in patients positive for the EGFR exon 21 L858R point mutation.OBJECTIVETo determine the clinical characteristics of patients with EGFR exon 21 L858R point mutation-positive NSCLC who are non-responders to EGFR-TKI therapy and the factors that predict response to EGFR-TKI therapy.METHODSPatients with NSCLC treated with EGFR-TKIs were evaluated for response after treatment, and those who responded were compared with those who did not respond.RESULTSOf 31 patients, 21 (67.7%) responded to EGFR-TKI therapy (the response group). There were significantly more programmed death ligand 1 (PDL1)-negative patients in the response group than in the non-response group. A significantly higher number of patients in the PDL1-positive group developed interstitial lung disease (ILD) after EGFR-TKI therapy than those in the PDL1-negative group.CONCLUSIONEGFR-TKI therapy is likely to be non-responsive in PDL1-positive patients with EGFR exon 21 L858R point mutation-positive NSCLC. The PDL1-positive group is at a high risk of developing ILD.

2023-09-15·Maedica - A Journal of Clinical Medicine

EGFR Mutated Non-Small Cell Lung Cancer Complicated by Cancer Associated Ischemic Stroke

作者: Satoh, Hiroaki ; Okauchi, Shinichiro ; Ohara, Gen ; Hasegawa, Sachie ; Hizawa, Nubuyuki ; Taguchi, Manato ; Kawakami, Takeshi

We describe herein two patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) who developed cancer-associated ischemic stroke (CAIS), infarction caused by thromboembolism in the central nervous system. Case 1 was a 63-year-old man with Exon 19 deletion type EGFR mutated lung adenocarcinoma presenting with CAIS. Case 2 was a 71-year-old woman with Exon 21 L858R type EGFR mutated lung adenocarcinoma who developed CAIS during chemotherapy after EGFR-tyrosine kinase inhibitor (TKI) resistance. Although there was no recurrence of CAIS in these patients, anticancer therapy could be hampered by the comorbidity of CAIS. This can develop anytime from before clinical manifestations of NSCLC to the next treatment after EGFR-TKI resistance. The development of CAIS should be noted in patients with EGFR mutated NSCLC, who have a promising long-term prognosis. Anticancer and anticoagulant therapies as well as rehabilitation are important for patients who develop CAIS. Establishment of measurement tests to detect CAIS before onset is desired.

2022-11-01·Cytopathology

Sequential small cell transformation and T790M mutation in an epidermal growth factor‐mutant lung adenocarcinoma: A rare occurrence with significant management implications

作者: Gupta, Parikshaa ; Khosla, Divya ; Srinivasan, Radhika ; Singh, Navneet ; Gupta, Nalini ; Bal, Amanjit ; Shastri, Malvika

AbstractBackgroundEpidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitor (TKI) resistance may be acquired via genotypic and/or phenotypic transformations. Herein, we report an extremely uncommon case with sequential small cell transformation and EGFR T790M mutation, in an elderly female with EGFR exon 21 L858R‐mutant lung adenocarcinoma, following treatment with a first‐generation EGFR‐TKI.CaseA 67‐year‐old female never‐smoker presented with a cough and dyspnoea of 2 months' duration. Computerised tomography revealed a 39 mm lesion in the upper lobe of the right lung with pleural effusion. Pleural fluid cytology revealed metastatic lung adenocarcinoma, and EGFR testing revealed exon 21 L858R mutation. She was started on gefitinib. After a progression‐free survival of 31 months, she presented with disease progression and multiple extra‐thoracic metastases. Fine needle aspiration cytology of a chest wall lesion revealed metastatic small cell carcinoma. EGFR testing on this aspirate revealed persistent L858R mutation only. In view of small cell transformation, chemotherapy (etoposide and carboplatin) was administered. After 4 months, ascitic fluid cytology revealed metastatic adenocarcinoma with persistent L858R mutation and an acquired T790M mutation (both detected on liquid biopsy as well) indicating amplification of the adenocarcinoma clone and regression of the small cell carcinoma clone. She was then initiated on osimertinib.ConclusionsThe index case highlights the significance of serial EGFR genotyping along with repeated tissue and/or blood sampling in the prompt detection of genetic and phenotypic resistance mechanisms to EGFR‐TKIs. Furthermore, it lends evidence in support of the upfront treatment approaches targeting the heterogeneity of acquired EGFR‐TKI resistance mechanisms.

项与 EGFR外显子21替代突变非小细胞肺癌相关的新闻（医药）

2024-10-08

·Pharma CMC

信达生物与奥赛康药业达成战略合作

10月8日，信达生物宣布与奥赛康药业签署合作协议，双方就第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）靶向药物利厄替尼片（奥壹新®）达成独家商业化合作。奥赛康药业将作为合作产品的上市许可持有人，负责合作产品的商业化生产及供货，并根据合作协议向信达生物支付销售推广服务费。信达生物取得合作产品在中国大陆地区的独家推广销售权，将按合作协议约定向奥赛康药业支付首付款、注册里程碑和销售里程碑款项。利厄替尼是具有自主知识产权、全新分子实体、活性显著的口服的第三代EGFR-TKI。目前，利厄替尼片（奥壹新®）的两项适应症的新药上市申请（NDA）在国家药品监督管理局（NMPA）审评审批中，分别为：既往经EGFR酪氨酸激酶抑制剂（TKI）治疗时或治疗后出现疾病进展，并且经检测确认存在EGFR T790M突变阳性，或原发性EGFR T790M突变阳性的局部晚期或转移性非小细胞肺癌成人患者的治疗；具有表皮生长因子受体（EGFR）外显子 19 缺失（19DEL）或外显子 21置换突变（L858R）的局部晚期或转移性非小细胞肺癌成人患者的一线治疗。在一项多中心、随机、双盲、阳性对照III期临床试验中，利厄替尼头对头吉非替尼一线治疗EGFR敏感突变的局部晚期或转移性非小细胞肺癌患者，达到主要研究终点。该III期临床研究的相关数据及分析计划在未来学术大会或学术期刊上发表。早先，利厄替尼在2022年美国临床肿瘤学会（ASCO）年会上以壁报的形式展示了其2b期临床研究结果。

临床3期ASCO会议引进/卖出申请上市

2024-08-21

·药明康德

不用化疗一线治疗肺癌，双特异性抗体联合疗法获FDA批准

强生（Johnson & Johnson）今天宣布，美国FDA批准其双特异性抗体Rybrevant（amivantamab）联合第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）口服药物Lazcluze（lazertinib）用于一线治疗经美国FDA批准检测证实带有EGFR外显子19缺失或外显子21中L858R替代突变的局部晚期或转移性非小细胞肺癌（NSCLC）成年患者。之前试验结果显示，与活性对照药物相比，Rybrevant与Lazcluze联合疗法可降低患者疾病进展或死亡风险达30%。这次美国FDA的批准主要是基于MARIPOSA临床3期研究的积极结果，该研究检视Rybrevant与Lazcluze联合疗法与活性对照TKI药物Tagrisso相比，用以一线治疗EGFR外显子19缺失或外显子21中L858R替代突变的局部晚期或转移性NSCLC患者的疗效与安全性。分析显示，Rybrevant与Lazcluze与活性对照药物相比，可将疾病进展或死亡风险降低30%，联合疗法与活性对照药物组患者的中位无进展生存期（PFS）分别为23.7个月与16.6个月。此外，联合疗法组的中位DOR比活性对照药物长9个月（25.8个月vs 16.7个月），这是该研究的次要终点。联合疗法的安全性与各个组分的已知安全性一致。 Rybrevant是一款人源化EGFR/MET双特异性抗体。它具有多重抗癌的作用机制，不但能够阻断EGFR和MET介导的信号传导，还可以引导免疫细胞靶向携带激活性和耐药性EGFR/MET突变和扩增的肿瘤。Rybrevant于2021年5月获得美国FDA的加速批准，用于治疗经FDA批准的检测发现EGFR外显子20插入突变、接受铂类化疗过程中或化疗后病情进展的局部晚期或转移性NSCLC成年患者。Lazcluze则是一种具高选择性、可穿透血脑屏障的第三代口服EGFR TKI。参考资料： [1] RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. Retrieved August 20, 2024 from https://www.jnj.com/media-center/press-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-approved-in-the-u-s-as-a-first-line-chemotherapy-free-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer 内容来源于网络，如有侵权，请联系删除。

加速审批临床结果免疫疗法

2024-07-11

·贝达药业

贝达药业CFT8919胶囊临床试验申请获受理

7月9日，贝达药业和C4 Therapeutics, Inc. （C4T）合作开发的CFT8919胶囊获得国家药品监督管理局签发的《受理通知书》（受理号：CXHL2400676 、 CXHL2400677）,拟用于携带 EGFR 突变的非小细胞肺癌患者适应症。 2023年12月，贝达药业获得中国NMPA批准开展CFT8919片剂临床试验，本次受理为胶囊剂的临床试验申请。 CFT8919是一种具有口服生物利用度的变构 BiDAC™ 降解剂,在临床前研究中，CFT8919在EGFR L858R驱动的NSCLC的体内外模型中具有活性，可靶向广泛的在靶耐药突变并有颅内活性，具有预防或治疗患者脑转移的潜力。CFT8919通过与L858R突变的变构位点结合，展示出良好的选择性，同时对像T790M或C797S突变的EGFR继发耐药突变有效。此外，CFT8919不仅对携带L858R单突变而且对奥希替尼、厄洛替尼耐药后产生的L858R继发耐药突变，均具有很好细胞增殖抑制活性，同时展示出良好的EGFR野生型选择性。贝达药业副总裁、项目总负责人王三虎表示，CFT8919胶囊IND申报获受理，是贝达和C4T双方项目团队共同努力的结果。本品有望为EGFR L858R 突变患者提供新的治疗选择，贝达将积极推进CFT8919的临床研究，期待能早日造福广大患者。贝达药业董事长丁列明博士表示，肺癌是贝达重点布局的优势领域。随着进一步的研究和开发，CFT8919胶囊有望成为EGFR外显子21（L858R）突变NSCLC治疗领域的重要突破，从而改善患者的生活质量。贝达会保持初心，聚焦未被满足的临床需求，不断创新突破，给患者带来新的希望，为健康中国建设添砖加瓦。内容来源于网络，如有侵权，请联系删除。