Ilourac (WX-0593) is a next-generation, potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), showing both systemic and central nervous system (CNS) efficacy in patients with ALK-positive non-small cell lung cancer (NSCLC). At the 2024 ESMO Congress, updated data from the INSPIRE study were presented in a poster session, showing continued progression-free survival (PFS) improvement with ilourac compared to crizotinib in advanced ALK-positive and ALK TKI-naive NSCLC patients. Safety findings were consistent with previous results, with no new safety concerns observed. In this article, Oncology Outlook invited Dr. Xiao Chen from The First Bethune Hospital of Jilin University to provide commentary on the updated data from this study (Abstract #1278P).

The INSPIRE study (NCT04632758) is an open-label, randomized, multi-center Phase III clinical trial aimed at evaluating the efficacy and safety of ilourac versus crizotinib in patients with locally advanced or metastatic ALK-positive NSCLC who had not previously received ALK TKI therapy. The primary endpoint is PFS as assessed by an Independent Review Committee (IRC) based on RECIST version 1.1. Secondary endpoints include investigator-assessed PFS, objective response rate (ORR), and safety.

Dr. Xiao Chen：Based on data analysis from the INTELLECT study, ilourac demonstrated an ORR of 69.9% in advanced NSCLC patients with ALK-positive disease who were resistant to crizotinib, with a median PFS of 19.8 months as assessed by the IRC, highlighting its efficacy and manageable safety profile.

In the initial interim analysis presented at the 2023 WCLC, ilourac significantly improved PFS compared to crizotinib in ALK-positive, advanced NSCLC patients who had not previously received ALK TKI therapy. This finding led to the National Medical Products Administration (NMPA) approval of ilourac on January 9, 2024, for the first-line treatment of patients with ALK-positive, locally advanced, or metastatic NSCLC.

With extended follow-up at the 2024 ESMO Congress, updated data from the INSPIRE study showed further extension of median PFS to 36.8 months for patients treated with ilourac, reducing the risk of disease progression or death by 69% compared to crizotinib. This demonstrates a continued PFS improvement in ALK-positive advanced NSCLC patients. Regarding safety, patients treated with ilourac experienced lower rates of muscle pain, nausea, constipation, and edema, and no new safety events were observed.

All patients in the INSPIRE study were from China, making it the largest randomized controlled trial (RCT) with head-to-head comparison against crizotinib among Asian patients across all ALK inhibitors currently on the market. These results provide more clinically relevant data for the Chinese population, solidifying ilourac as a promising first-line treatment option for more ALK-positive advanced NSCLC patients in the future.

Reference

[1]Shi Y, Chen J, Yang R, Wu H, Wang Z, Yang W, Cui J, Zhang Y, Liu C, Cheng Y, Liu Y, Shan J, Wang D, Yang L, Hu C, Zhao J, Cao R, Tan B, Xu K, Si M, Li H, Mao R, Li L, Kang X, Wang L. Iruplinalkib (WX-0593) Versus Crizotinib in ALK TKI-Naive Locally Advanced or Metastatic ALK-Positive NSCLC: Interim Analysis of a Randomized, Open-Label, Phase 3 Study (INSPIRE). J Thorac Oncol. 2024 Jun;19(6):912-927. doi: 10.1016/j.jtho.2024.01.013. Epub 2024 Jan 25. PMID: 38280448.

[2]Shi Y, Chen J, Zhang H, Zhang Z, Zhang Y, Wang Z, Zhang S, Zhao J, Liu C, Wang X, Zhao Y, Hu C, Yang L, Hao X, Wang L, Liu Y, Yu Y, Zhao J, Wang M, Zhang L, Sun S, Hu Y, Gu K, Hang X, Shan J, Zhang Y, Tan B, Yang W, Yang R, Si M, Geng H, Li H, Kang X. Efficacy and safety of iruplinalkib (WX-0593) in ALK-positive crizotinib-resistant advanced non-small cell lung cancer patients: a single-arm, multicenter phase II study (INTELLECT). BMC Med. 2023 Feb 24;21(1):72. doi: 10.1186/s12916-023-02738-5. PMID: 36829154; PMCID: PMC9960473.

[3]Update of the INSPIRE study: Iruplinalkib versus crizotinib in ALK TKI-naïve locally advanced or metastatic ALK+ non-small cell lung cancer (NSCLC)（2024 ESMO 1278P）

Dr. Xiao Chen

  • Vice Chair, Department of Oncology, The First Hospital of Jilin University
  • Chief Physician, PhD in Medicine, Master’s Supervisor
  • Executive Member, Youth Committee of the Tumor Chemotherapy Specialty, Chinese Medical Education Association
  • Executive Member, Cancer Early Screening, Early Diagnosis, and Early Treatment Committee, Beijing Tumor Prevention Research Association
  • Member, Cytogenetics and Genomics Group, Chinese Medical Association
  • Member, Thoracic Oncology Committee, China International Exchange and Promotive Association for Medical and Health Care
  • Member, Tumor Immunotherapy Committee, China International Exchange and Promotive Association for Medical and Health Care
  • Member, Tumor Supportive Care Committee, Chinese Anti-Cancer Association
  • Member, Difficult Tumor Specialty Committee, Chinese Medical Education Association
  • Member, Tumor Targeted Therapy Technology Committee, Chinese Biomedical Engineering Society
  • Deputy Chair, Oncology Committee, Jilin Provincial Society of Research-Oriented Hospitals
  • Executive Member, Tumor Palliative Care Committee, Jilin Provincial Life Care Association
  • Member, Medical Immunology Association, Jilin Province
  • Editorial Board Member, Electronic Journal of Tumor Metabolism and Nutrition

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Last updated on 2024.10.17