Details

Autor(en) / Beteiligte

• Shi, Yuankai
• Chen, Jianhua
• Zhang, Helong
• Zhang, Zhihong
• Zhang, Yiping
• Wang, Zhehai
• Zhang, Shucai
• Zhao, Jian
• Liu, Chunling
• Wang, Xiuwen
• Zhao, Yanqiu
• Hu, Changlu
• Yang, Lei
• Hao, Xuezhi
• Wang, Lin
• Si, Meimei
• Ge, Mingjing
• Geng, Huaize

Titel

A phase II trial of ALK/ROS1 tyrosine kinase inhibitor WX-0593 (iruplinalkib) in ALK -positive and crizotinib-resistant advanced non–small cell lung cancer

Ist Teil von

• Journal of clinical oncology, 2022-06, Vol.40 (16_suppl), p.9073-9073

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 9073 Background: This single-arm, multicenter phase II trial aimed to evaluate the efficacy and safety of second generation ALK/ROS1 TKI WX-0593 (iruplinalkib) in advanced ALK/ ROS1-positive non-small cell lung cancer (NSCLC). We reported the results from the crizotinib-resistant ALK-positive cohort. Methods: Patients aged ≥18 years, with histologically or cytologically confirmed ALK-positive NSCLC, progression on ≥12-week crizotinib treatment, ≥one measurable lesion according to RECIST v1.1, and ECOG PS of 0 to 2 were eligible. Patients received oral WX-0593 180 mg once daily (with a 7-day lead-in period at 60 mg once daily). The primary endpoint was confirmed overall response rate (ORR) by independent review committee (IRC) per RECIST v1.1. Secondary endpoints included confirmed disease control rate (DCR) by IRC, ORR, DCR, duration of response (DoR), progression-free survival (PFS), time to progression (TTP), intracranial ORR (iORR) per RANO-brain metastases criteria by investigator (INV), overall survival (OS), safety, and C max,ss . Results: Between August 7, 2019 and October 30, 2020, totally 146 patients were enrolled. The data cutoff date was March 10, 2021. The median follow-up was 9.3 months (IQR 6.3-14.1). 90 (61.6%) patients had brain metastases, of which 41 (46%) had measurable intracranial lesions and 20 (22%) received prior radiotherapy to brain. 56 (38.4%) patients received prior chemotherapy. The IRC-assessed ORR was 67.8% (95% CI 59.6%-75.3%). Efficacy data were detailed in the Table. Additionally, subgroup analyses indicated IRC-assessed ORR were slightly higher in the patients without brain metastases (79% vs 61%) or prior radiotherapy to brain (66% vs 45%). Patients with prior chemotherapy or not had similar results (71% vs 66%). The iORR was 63% (95% CI 47%-78%) in pts with measurable intracranial lesions. OS data were immature. 134 (91.8%) of 146 experienced treatment-related adverse events (TRAEs). The most common TRAEs were AST increased (60 [41.1%]), ALT increased (52 [35.6%]), and blood creatine phosphokinase increased (49 [33.6%]). Dose reduction and discontinuation due to TRAE, and serious TRAEs occurred in 15 (10.3%), three (2.1%), and six (4.1%), respectively. No treatment-related death was reported. Drug concentration reaches steady state at Day 21 (C max,ss =255.4 ng/mL). Conclusions: WX-0593 showed promising activity against ALK-positive NSCLC after crizotinib resistance and favorable safety profile, demonstrating WX-0593 could be a new treatment option for this patient population. Clinical trial information: NCT04641754. [Table: see text]