{"title":"Iruplinalkib for G1202R-mutant non-small cell lung cancer with anaplastic lymphoma kinase double fusion failed to alectinib: a case report.","authors":"Guangjian Yang, Jiaqi Hu, Runze Liu, Pei Li, Linke Yang, Xiaoyong Tang, Luokun Wang","doi":"10.1097/CAD.0000000000001695","DOIUrl":null,"url":null,"abstract":"<p><p>The novel and highly selective anaplastic lymphoma kinase ( ALK ) inhibitor iruplinalkib showed potent activity and manageable safety profiles in patients with ALK -rearranged non-small cell lung cancer (NSCLC). However, the evidence of iruplinalkib for uncommon ALK double fusion and secondary G1202R resistance mutation is limited. Here, we report a case of a 36-year-old male with metastatic NSCLC harboring uncommon TTC7A - ALK and EML4 - ALK double fusion. Alectinib as first-line therapy showed partial response, with a progression-free survival (PFS) of 20 months. When his disease progressed, the ALK secondary G1202R resistance mutation was identified. His metastatic paraesophageal lymph node decreased during iruplinalkib treatment, achieving an ongoing PFS benefit for 10 months. Treatment-related adverse events of iruplinalkib were grade 1 hypercholesterolemia and hypertriglyceridemia. The modeling simulation revealed that the G1202R mutation exerted little effect on the binding of iruplinalkib. Iruplinalkib showed potency to G1202R because of its unique chemical structure and removal of steric clashes, which might be a promising option for ALK -rearranged NSCLC patients with G1202R resistance mutation.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"432-437"},"PeriodicalIF":1.8000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969368/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anti-Cancer Drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CAD.0000000000001695","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/17 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The novel and highly selective anaplastic lymphoma kinase ( ALK ) inhibitor iruplinalkib showed potent activity and manageable safety profiles in patients with ALK -rearranged non-small cell lung cancer (NSCLC). However, the evidence of iruplinalkib for uncommon ALK double fusion and secondary G1202R resistance mutation is limited. Here, we report a case of a 36-year-old male with metastatic NSCLC harboring uncommon TTC7A - ALK and EML4 - ALK double fusion. Alectinib as first-line therapy showed partial response, with a progression-free survival (PFS) of 20 months. When his disease progressed, the ALK secondary G1202R resistance mutation was identified. His metastatic paraesophageal lymph node decreased during iruplinalkib treatment, achieving an ongoing PFS benefit for 10 months. Treatment-related adverse events of iruplinalkib were grade 1 hypercholesterolemia and hypertriglyceridemia. The modeling simulation revealed that the G1202R mutation exerted little effect on the binding of iruplinalkib. Iruplinalkib showed potency to G1202R because of its unique chemical structure and removal of steric clashes, which might be a promising option for ALK -rearranged NSCLC patients with G1202R resistance mutation.
期刊介绍:
Anti-Cancer Drugs reports both clinical and experimental results related to anti-cancer drugs, and welcomes contributions on anti-cancer drug design, drug delivery, pharmacology, hormonal and biological modalities and chemotherapy evaluation. An internationally refereed journal devoted to the fast publication of innovative investigations on therapeutic agents against cancer, Anti-Cancer Drugs aims to stimulate and report research on both toxic and non-toxic anti-cancer agents. Consequently, the scope on the journal will cover both conventional cytotoxic chemotherapy and hormonal or biological response modalities such as interleukins and immunotherapy. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.