https://scholars.lib.ntu.edu.tw/handle/123456789/557702
標題: | Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial | 作者: | CHIH-HSIN YANG Camidge D.R. Yang C.-T. Zhou J. Guo R. Chiu C.-H. Chang G.-C. Shiah H.-S. Chen Y. Wang C.-C. Berz D. Su W.-C. Yang N. Wang Z. Fang J. Chen J. Nikolinakos P. Lu Y. Pan H. Maniam A. Bazhenova L. Shirai K. Jahanzeb M. Willis M. Masood N. Chowhan N. Hsia T.-C. Jian H. Lu S. |
關鍵字: | EGFR T790M mutation; Epidermal growth factor receptor; non–small cell lung cancer; phase I trial; safety | 公開日期: | 2020 | 出版社: | Elsevier Inc. | 卷: | 15 | 期: | 12 | 起(迄)頁: | 1907-1918 | 來源出版物: | Journal of Thoracic Oncology | 摘要: | Introduction: Almonertinib (HS-10296) is a novel, third-generation EGFR tyrosine kinase inhibitor (EGFR TKI) that targets both EGFR-sensitizing and T790M resistance mutations. This first-in-human trial aimed to evaluate the safety, efficacy, and pharmacokinetics of almonertinib in patients with locally advanced or metastatic EGFR mutation-positive NSCLC that had progressed after pevious EGFR TKI therapy. Methods: This phase 1, open-label, multicenter clinical trial (NCT0298110) included dose-escalation (55, 110, 220, and 260 mg) and dose-expansion cohorts (55, 110, and 220 mg) with once daily oral administration of almonertinib. In each expansion cohort, tumor biopsies were obtained for the determination of EGFR T790M status. The safety, tolerability, antitumor activity, and pharmacokinetics of almonertinib were evaluated. Results: A total of 120 patients (26 patients in the dose-escalation cohort and 94 patients in the dose-expansion cohort) were enrolled. The maximum tolerated dose was not defined in the dose-escalation phase; the 260 mg regimen was not further evaluated in the dose-expansion phase owing to safety concerns and saturation of exposure. The most common treatment-related grade greater than or equal to 3 adverse events were increased blood creatine phosphokinase (10%) and increased alanine aminotransferase (3%). Among 94 patients with the EGFR T790M mutation in the dose-expansion cohort, the investigator-assessed objective response rate and disease control rate were 52% (95% confidence interval [CI]: 42–63) and 92% (95% CI: 84–96), respectively. Median progression-free survival was 11.0 months (95% CI: 9.5–not reached) months. Conclusions: Almonertinib is safe, tolerable and effective for patients with locally advanced or metastatic NSCLC harboring the EGFR T790M mutation who were pretreated with EGFR TKIs. ? 2020 International Association for the Study of Lung Cancer |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092734124&doi=10.1016%2fj.jtho.2020.09.001&partnerID=40&md5=ab38759a005aeeeb04af74604652377f https://scholars.lib.ntu.edu.tw/handle/123456789/557702 |
ISSN: | 1556-0864 | DOI: | 10.1016/j.jtho.2020.09.001 | SDG/關鍵字: | afatinib; alanine aminotransferase; almonertinib; antineoplastic agent; aspartate aminotransferase; creatine kinase; dacomitinib; dbpr 112; epidermal growth factor receptor; epidermal growth factor receptor kinase inhibitor; erlotinib; gefitinib; hs 10296; icotinib; methionine; naquotinib; olmutinib; osimertinib; rociletinib; threonine; unclassified drug; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; protein kinase inhibitor; adult; advanced cancer; aged; alanine aminotransferase blood level; anemia; antineoplastic activity; area under the curve; Article; aspartate aminotransferase blood level; backache; cancer chemotherapy; cancer control; cancer radiotherapy; cancer surgery; cohort analysis; constipation; controlled clinical trial; controlled study; coughing; creatine kinase blood level; diarrhea; dizziness; dose response; drug dose escalation; drug dose reduction; drug efficacy; drug half life; drug safety; drug tolerability; drug withdrawal; EGFR gene; female; gene mutation; heart ventricle extrasystole; human; human tissue; interstitial lung disease; leukocyte count; limb pain; lung adenocarcinoma; major clinical study; male; maximum plasma concentration; maximum tolerated dose; metastasis; multicenter study; multiple drug dose; nausea; non small cell lung cancer; open study; phase 2 clinical trial; pneumonia; priority journal; progression free survival; pruritus; rash; side effect; single drug dose; sinus bradycardia; tachycardia; thorax pain; upper respiratory tract infection; urinary tract infection; clinical trial; genetics; lung tumor; mutation; non small cell lung cancer; phase 1 clinical trial; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors |
顯示於: | 腫瘤醫學研究所 |
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