Merck KGaA said Wednesday that Tepmetko (tepotinib) was approved by the Japanese Ministry of Health, Labour and Welfare for the treatment of patients with unresectable, advanced or recurrent non-small-cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations. The company noted that this is the first regulatory clearance globally for an oral MET inhibitor in this indication.
"With Tepmetko, we are pleased to offer the first approved MET inhibitor in Japan," remarked Belén Garijo, CEO of Merck's healthcare division, with the company planning to seek US clearance of the drug this year. Merck noted that a companion diagnostic featuring both liquid and tissue biopsy capabilities to identify METex14 skipping alterations among patients with NSCLC gained Japanese approval this month, with the test developed under a partnership with ArcherDX.
Approval of Tepmetko in Japan was supported by data from the Phase II VISION study, which enrolled 99 NSCLC patients, including 15 Japanese subjects, with METex14 skipping alterations. The ongoing trial assessed objective response rate (ORR) as the primary endpoint, with the once-daily treatment demonstrating "meaningful benefit" across different lines of treatment, according to Merck. Specifically, the ORR was 42.4% in patients identified by liquid biopsy (LBx) or tissue biopsy (TBx), while median duration of response was 12.4 months for both LBx-identified and TBx-identified patients.
A safety analysis of 130 patients showed that Tepmetko was well tolerated, with the most frequent treatment-related adverse events (TRAEs) of any grade being peripheral oedema, nausea and diarrhoea. The company noted that 11 patients permanently discontinued the VISION trial as a result of TRAEs.
Tepmetko previously received orphan drug designation from Japanese regulators to treat patients with NSCLC harbouring MET gene alterations. Meanwhile, in the US, the FDA has designated the drug a breakthrough therapy for patients with metastatic NSCLC harboring METex14 skipping alterations who have progressed following platinum-based cancer treatment. Merck's compound is also being investigated in the INSIGHT 2 study in combination with AstraZeneca's tyrosine kinase inhibitor (TKI) Tagrisso (osimertinib) to treat EGFR-mutated, MET amplified, locally-advanced or metastatic NSCLC that has acquired resistance to prior EGFR TKI.
Earlier this year, the FDA granted priority review to a filing from Novartis regarding the oral MET inhibitor capmatinib in METex14-mutated lung cancer. That submission is supported by data from the Phase II GEOMETRY mono-1 study, in which capmatinib demonstrated an overall response rate of 67.9% and 40.6% among treatment-naïve and previously treated patients, respectively. For related analysis, see ViewPoints: Novartis takes lead in METex14 lung cancer race.
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