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29 patients with NSCLCs harboring METex14 mutations, including 18 from the compassionate-use cohort and 11 from the phase II clinical trial (ChiCTR2100045803), were treated with ensartinib (225 mg once daily)….In the compassionate-use cohort of 18 patients, 1 patient achieved CR, 11 exhibited PR, and 5 had stable disease (SD) (Fig. 1B and C, and S1). The ORR was 67% [12/18, 95% confidence interval (CI), 43–91] and the DCR was 94% (17/18, 95% CI, 83–106). In the phase II cohort, among the 11 evaluable patients, 8 had confirmed PR and 2 had SD; The ORR and DCR were 73% (8/11, 95% CI, 41–104) and 91% (10/11, 95% CI, 71–111), respectively. (Fig. 1B and C).

Molecular dynamic simulations revealed that ensartinib exhibited favorable binding to c-MET. Ensartinib was highly effective in inhibiting the kinase activity of the MET exon 14 deletion protein (IC50 = 7.9 nM). Furthermore, ensartinib potently suppressed the MET pathway and the growth of Hs746T cells that were subcutaneously implanted into mice. Most importantly, of 17 patients with 14 different types of MET exon 14 skipping mutations undergoing ensartinib treatment, 1 (6%) showed a complete response, 11 (65%) achieved a partial response, and 4 (24%) exhibited stable disease. Thus, the objective response rate (ORR) was 71% and the disease control rate (DCR) was 94%, and the ORR in MET-TKI naive patients was even higher (12/15, 80%). These results provide the first evidence that ensartinib exhibits both preclinical and clinical antitumor activity against MET exon 14 skipping mutations with the potential of strong intracranial efficacy...

We assessed the antitumor activity of ensartinib against MET exon 14 skipping mutations in NSCLCs in vitro and in vivo....and the patient who received ensartinib showed promising clinical benefit.

We assessed the antitumor activity of ensartinib against MET exon 14 skipping mutations in NSCLCs in vitro and in vivo....ensartinib potently inhibited the viability of the patient-derived organoids (PDOs) from a NSCLC patient harboring MET exon 14 skipping mutation by blocking the phosphorylation of the MET pathway...