Release of ctDNA analysis results of Betta Pharmaceuticals' Phase 2 study of Ensatinib

On March 1, Betta Pharmaceuticals issued a press release stating that the internationally renowned oncology journal "Journal of Thoracic Oncology" (Journal of Thoracic Oncology, JTO) published online the Phase 2 clinical study of Ensatinib capsules (BTP-42322 study) The results of the dynamic circulating tumor cell DNA (ctDNA) detection and analysis results of the anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients taking Ensatinib capsules to develop drug resistance, revealing Part of the mechanism by which tumors evolve to drug resistance during the treatment of Ensatinib can effectively guide further research directions and clinical treatment practices.

Ensatinib is a new and powerful, highly selective new-generation ALK inhibitor jointly developed by Betta Pharmaceuticals and its subsidiary Xcovery Holdings.

The research published online in JTO was led by Professor Zhang Li, director of Sun Yat-sen University Cancer Center.

ALK fusion genotype is a common target in NSCLC.

It has been reported in the literature that the resistance mechanisms of different ALK inhibitors are different, and bypass activation and pathological type conversion are known resistance mechanisms.

In this study, patients’ peripheral blood ctDNA was obtained, and NGS gene sequencing methods were used to detect a large number of resistance sites including ALK kinase region mutations such as L1196M, G1269A, C1156Y, G1202R, E1210K, TP53 and others that have been reported in the literature.

The results show that TP53 is an important prognostic factor in the non-ALK-dependent pathway.

The results of detection and analysis of drug resistance sites on the ALK-dependent pathway show that the main drug resistance sites of Ensatinib on the ALK pathway are G1269A, G1202R and E1210K mutations, which may be one of the reasons for drug resistance.