A Novel Intergenic Gene Between and - Fusion Responds to TKI WX-0593 in Lung Adenocarcinoma: A Case Report.

Background: Expanding the druggable novel anaplastic lymphoma kinase () fusions list is crucial to the precise treatment of patients with cancer with positive fusions. The fusions accounted for a substantial proportion of fusions. However, they were typically considered of limited clinical significance due to the obscure functional partners. In this case report, a patient carrying fusion presents an excellent outcome after taking the new second-generation tyrosine kinase inhibitor (TKI) candidate, WX-0593.

Case Presentation: A 47-year-old Chinese female patient diagnosed with IVB lung adenocarcinoma was admitted to the hospital with large dimension lesions in the left lobe of the lung. After 1 week of first line chemotherapy, no response was found. A novel rearrangement generated by a fusion of the intergenic region between and to the intron 19 of was presented after next-generation sequencing and was further confirmed by Sanger's sequencing. High expression of was revealed by immunohistochemistry. The patient was directed to engage in phase III clinical trial (NCT04632758) and received an orally active second-generation inhibitor WX-0593. Over the course of 17 months, the partial response was obtained without significant side effects.

Conclusion: In summary, a patient with non-small cell lung cancer harboring a novel fusion, whose intergenic breakpoint was located between and , benefited from a potent TKI candidate WX-0593. This finding extended the scope of targetable fusions. More importantly, it highlighted the advantages of next-generation sequencing in identifying rare but functional fusions, which eventually benefit patients.