Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Discussion – NSCLC, metastatic

6131 - Safety and efficacy of WX-0593 in ALK-positive or ROS1-positive non-small cell lung cancer

Date

29 Sep 2019

Session

Poster Discussion – NSCLC, metastatic

Presenters

Yuan-Kai Shi

Citation

Annals of Oncology (2019) 30 (suppl_5): v602-v660. 10.1093/annonc/mdz260

Authors

Y. Shi1, J. Fang2, S. Zhang3, Y. Liu4, L. Wang5, M. Si6, M. Ge6, H. Geng6

Author affiliations

  • 1 Department Of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100021 - Beijing/CN
  • 2 Department Of Thoracic Oncology Ii, Peking University Cancer Hospital & Institute, Beijing/CN
  • 3 Department Of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing/CN
  • 4 Department Of Medical Oncology, The First Hospital of China Medical University,, Shenyang/CN
  • 5 Department Of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing/CN
  • 6 Clinical Reserch, Qilu Pharmaceutical Co.,Ltd, Jinan/CN

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 6131

Background

WX-0593 is a potent ALK inhibitor against ALK and ROS1 rearrangement and a series of crizotinib (CRZ)-resistant mutants. We explored the safety and efficacy of WX-0593 in patients (pts) diagnosed with ALK+ or ROS-1+ malignancies, including non-small cell lung cancer (NSCLC).

Methods

In this ongoing phase I, dose-escalation, multicenter trial (NCT03389815), 54 pts (third-grade class-A hospital confirmed ALK+ or ROS-1+) received WX-0593 (30, 60, 90, 120, 180, 240 or 300 mg) orally once daily until disease progression or unacceptable toxicity. Activity and safety were evaluated.

Results

From 25 September 2017 to 26 December 2018, 54 pts were enrolled, including 46 with ALK+ NSCLC, 10 with ROS1+ NSCLC (2 with both ALK+ and ROS1+, 38.9% with prior CRZ, 9.3% with prior CRZ and second generation ALK inhibitors). Grade 3 QTc prolongation reported in 300 mg cohort was identified as dose-limiting toxicity (DLT). Treatment-emergent adverse events (TAEs) associated with WX-0593 in > 20% of pts include: hypercholesterolemia (40.7%), nausea (40.7%), hypertension (37.0%) increased ALT (31.5%), increased AST (29.6%), hypertriglyceridemia (25.9%), hyperlipidemia (25.9%), vomiting 25.9%. Serious adverse events (SAE) occurred in 6 pts (11.1%). No treatment related death occurred. 2 pts (3.7%) had SAE related with WX-0593 treatment, including increased ALT (dose of 180 mg), increased AST (dose of 180 mg) and chronic heart failure (dose of 300 mg). For ALK+ NSCLC (n=46), objective response rate (ORR) was 29/44 (65.9%). The ORR in CRZ-naive pts was 17/21 (81.0%), 8/18 (44.4%) in CRZ pre-treated pts. ORR was 3/10 (30.0%) in ROS1+ NSCLC pts. By 26 December 2018, median progression-free survival was not reached, 39 patients remained on WX0593 treatment.Table:

1485PD Objective response rate in ALK-positive and ROS1-positive NSCLC patients

ORR, n / m (%)30mg N = 360mg N = 390mg N = 8120mg N = 11180mg N = 13240mg N = 13300mg N = 3total
ALK+NSCLC
all pts2/2 (100.0)2/3 (66.7)2/5 (40.0)8/10 (80.0)7/10 (70.0)7/11 (63.6)1/3 (33.3)29/44 (65.9)
CRZ-naive pts2/2 (100.0)2/3 (66.7)06/7 (85.7)3/4 (75.0)3/4 (75.0)1/1 (100.0)17/21 (81.0)
pts with prior CRZ002/4 (50.0)1/2 (50.0)3/5 (60.0)2/5 (40.0)0/28/18 (44.4)
pts with prior CRZ and other ALK inhibitor000/11/1 (100.0)1/1 (100.0)2/2 (100.0)04/5 (80.0)
ROS1+NSCLC
all pts0/101/3 (33.3%)0/12/3 (66.7%)0/203/10 (30.0%)

Conclusions

This study revealed the antitumor activity of WX-0593 in ALK- or ROS-positive NSCLC. Safety profile was acceptable. A phase II trial to evaluate the ORR of 120 mg and 180 mg once daily is ongoing.

Clinical trial identification

NCT03389815.

Editorial acknowledgement

Legal entity responsible for the study

Qilu Pharmaceutical Co., Ltd.

Funding

Qilu Pharmaceutical Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.