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

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

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.