In:
BMC Medicine, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2023-02-24)
Abstract:
Iruplinalkib (WX-0593) is an anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor. Here we reported the single-arm, phase II study (INTELLECT) results of the efficacy and safety of iruplinalkib for ALK -positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC) patients. Methods ALK -positive crizotinib-resistant advanced NSCLC patients aged ≥18 years, with Eastern Cooperative Oncology Group performance status of 0–2 were eligible. Patients received iruplinalkib 180 mg orally once daily for a 21-day cycle with a 7-day lead-in phase at 60 mg orally once daily. The primary endpoint was the independent review committee (IRC)-assessed objective response rate (ORR). Results From August 7, 2019, to October 30, 2020, 146 patients were included. As of the data cut-off date on November 30, 2021, the median follow-up time was 18.2 months (95% confidence interval [CI] 16.8–18.8). IRC-assessed ORR and disease control rate (DCR) were 69.9% (95% CI 61.7–77.2%) and 96.6% (95% CI 92.2–98.9%), respectively. Investigator-assessed ORR and DCR were 63.0% (95% CI 54.6–70.8%) and 94.5% (95% CI 89.5–97.6%), respectively. Investigator-assessed median duration of response and progression-free survival (the same as median time to progression) were 13.2 months (95% CI 10.4–17.7) and 14.5 months (95% CI 11.7–20.0), respectively. Corresponding IRC-assessed results were 14.4 months (95% CI 13.1–not evaluable [NE] ), 19.8 months (95% CI 14.5–NE), and NE (95% CI 14.5–NE), respectively. Investigator-assessed intracranial ORRs were 46% (41/90, 95% CI 35–56%) in patients with central nervous system metastases and 64% (27/42, 95% CI 48–78%) in patients with measurable intracranial lesions. Overall survival data were immature. Treatment-related adverse events (TRAEs) occurred in 136/146 (93.2%) patients. The most common TRAEs were aspartate aminotransferase increased (63 [43.2%]), alanine aminotransferase increased (54 [37.0%] ), and blood creatine phosphokinase increased (51 [34.9%]). Dose interruption, reduction, and discontinuation due to TRAEs occurred in 21 (14.4%), 16 (11.0%), and four (2.7%) patients, respectively. Conclusions In this study, iruplinalkib (WX-0593) demonstrated favorable efficacy and manageable safety profiles in patients with ALK -positive crizotinib-resistant advanced NSCLC. Iruplinalkib could be a new treatment option for this patient population. Trial registration Center for Drug Evaluation of National Medical Products Administration of China: CTR20190789, registered on April 28, 2019; ClinicalTrials.gov: NCT04641754, registered on November 24, 2020.
Type of Medium:
Online Resource
ISSN:
1741-7015
DOI:
10.1186/s12916-023-02738-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2131669-7
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