MHRA Grants Conditional Approval to Merck’s MET Inhibitor Tepmetko for NSCLC Patients with METex14 Skipping Mutations

Compiled and translated by | Fan Dongdong

Recently, the UK Medicines and Healthcare products Regulatory Agency (MHRA) announced the conditional approval of Merck's MET inhibitor Tepmetko (tepotinib) for the treatment of certain patients with non-small cell lung cancer (NSCLC). The drug is indicated specifically for adult patients with advanced NSCLC harboring mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping alterations.

The MHRA's decision to approve Tepmetko was primarily based on the results of the Phase II VISION study, which evaluated the efficacy of Tepmetko monotherapy in patients with advanced or metastatic NSCLC harboring MET exon 14 skipping alterations. Merck evaluated the efficacy of the therapy in 146 patients, and based on an independent review of the combined biopsy cohort (liquid biopsy + tissue biopsy), the objective response rate (ORR) among patients treated with Tepmetko was 46%.

Tepmetko is an oral MET kinase inhibitor developed in-house by Merck. This therapy potently and highly selectively inhibits oncogenic signaling driven by MET gene alterations (including MET exon 14 skipping alterations, MET amplification, and MET protein overexpression), and is therefore considered to have the potential to improve patient clinical outcomes. In addition to NSCLC, Merck is also actively evaluating Tepmetko in combination with novel therapies for other oncology indications.

In July this year, the UK MHRA issued a positive scientific opinion regarding Merck KGaA’s targeted cancer drug Tepmetko for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations. NSCLC is the most common type of lung cancer, accounting for over 80% of diagnosed lung cancer cases. Among these cases, approximately 3% to 4% of patients exhibit the METex14 alteration. Compared with other NSCLC subtypes, patients with this alteration have a poorer clinical prognosis.

Notably, the approval of Tepmetko was granted through the ORBiS Project, a regulatory pathway coordinated by the U.S. Food and Drug Administration (FDA). This initiative is designed to enable the concurrent review and approval of promising cancer therapies in collaboration with regulatory authorities in up to six countries, including the UK's MHRA. The objective is to accelerate patient access to innovative cancer treatments that offer potential advantages over existing therapies available globally.

In March 2020, the drug received approval from Japan’s Ministry of Health, Labour and Welfare (MHLW), making Tepmetko the world’s first oral MET inhibitor approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients harboring MET gene alterations. This February, Tepmetko achieved a regulatory breakthrough in the US market, obtaining accelerated approval from the U.S. Food and Drug Administration (FDA).

Reference Source:

MHRA backs Merck’s MET inhibitor Tepmetko