General Information

Tepmetko (tepotinib) is a kinase inhibitor.

Tepmetko is specifically indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal epithelial transition (MET) exon 14 skipping alterations.

Tepmetko is supplied as a tablet for oral administration. The recommended dosage is 450 mg orally once daily with food until disease progression or unacceptable toxicity. Tepmetko should be taken at approximately the same time every day and the tablets should be swallowed whole. Do not chew, crush or split tablets. Do not to make up a missed dose within 8 hours of the next scheduled dose. If vomiting occurs after taking a dose of Tepmetko, advise patients to take the next dose at the scheduled time.

Clinical Trials

Tepmetko was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial.

The approval was based on results from the pivotal Phase II VISION study.

VISION is an ongoing pivotal Phase II, multicenter, multi-cohort, single-arm, non-randomized, open-label study investigating tepotinib as monotherapy in 152 patients with a median age of 73 years with advanced or metastatic non-small cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations. Eligible patients were required to have advanced or metastatic NSCLC harboring METex14 skipping alterations, epidermal growth factor receptor (EGFR) wild-type and anaplastic lymphoma kinase (ALK) negative status, at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. Patients received Tepmetko 450 mg once daily until disease progression or unacceptable toxicity. The major efficacy outcome measure is overall response rate (ORR) according to RECIST version 1.1 as assessed by a blinded independent review committee (BIRC). An additional efficacy outcome measure was duration of response (DOR) by BIRC.

In the study, Tepmetko demonstrated an overall response rate of 43% in both treatment-naïve and previously treated patients (n=83). Median duration of response (DOR) was 10.8 months and 11.1 months among treatment-naïve and previously treated patients, respectively. Duration of response of six months or more occurred among 67% of treatment-naïve patients and 75% of previously treated patients, and duration of response of nine months or more occurred among 30% of treatment-naïve patients and 50% of previously treated patients.

Mechanism of Action

Tepotinib is a kinase inhibitor that targets MET, including variants with exon 14 skipping alterations. Tepotinib inhibits hepatocyte growth factor (HGF)-dependent and -independent MET phosphorylation and MET-dependent downstream signaling pathways. Tepotinib also inhibited melatonin 2 and imidazoline 1 receptors at clinically achievable concentrations. In vitro, tepotinib inhibited tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent tumor cells. In mice implanted with tumor cell lines with oncogenic activation of MET, including METex14 skipping alterations, tepotinib inhibited tumor growth, led to sustained inhibition of MET phosphorylation, and, in one model, decreased the formation of metastases.