Merck KGaA announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Tepmetko (tepotinib) for the treatment of patients with unresectable, advanced or recurrent non-small cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations. Tepmetko is administered 500 mg once daily as two 250 mg tablets. This is the first regulatory approval globally for an oral MET inhibitor indicated for the treatment of advanced NSCLC harboring MET gene alterations. Tepmetko was previously granted SAKIGAKE ’fast-track’ designation and orphan drug designation by the MHLW.
The approval of Tepmetko (tepotinib) in Japan is supported by data from 99 patients (including 15 Japanese patients) with NSCLC with METex14 skipping alterations enrolled in the ongoing single-arm Phase II VISION study. The primary endpoint, objective response rate as assessed by an Independent Review Committee (IRC), was 42.4% (95% CI: 32.5, 52.8) in patients identified by liquid biopsy (LBx) or tissue biopsy (TBx). The median duration of response based on independent assessment was 12.4 months for both LBx-identified (95% CI: 8.4 months, not evaluable) and TBx-identified patients (95% CI: 9.7 months, NE). In a safety analysis of 130 patients, tepotinib was well-tolerated; the most frequent treatment-related adverse events (TRAEs) of any grade were peripheral edema (53.8%), nausea (23.8%) and diarrhea (20.8%). TRAEs led to permanent discontinuation in 11 patients (8.5%).
Merck KGaA has a strategic partnership with ArcherDX to develop a companion diagnostic featuring both liquid and tissue biopsy capabilities to identify METex14 skipping alterations among patients with NSCLC with high precision and accuracy prior to treatment. The companion diagnostic received approval by MHLW in March 2020, and it is the first and only companion diagnostic to be approved for the detection of MET gene alterations.
ArcherDX is a genomic analysis company dedicated to democratizing precision oncology through a suite of products and services that are accurate, personal, actionable and easy to use in local settings. Discovered in-house at Merck, tepotinib is an oral MET inhibitor that is designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, including both METex14 skipping alterations and MET amplifications, or MET protein overexpression.
Comment: Merck KGaA plans to file tepotinib for regulatory review with the FDA in 2020.