TEPMETKO

What it is

TEPMETKO is a film-coated tablet containing 225 mg tepotinib (equivalent to 250 mg tepotinib hydrochloride monohydrate). Tepotinib is a Type I adenosine triphosphate (ATP)-competitive small molecule inhibitor of MET. Tepotinib inhibits HGF-dependent and independent MET phosphorylation and MET-dependent downstream signalling including the phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinase/extracellular-signal regulated kinase pathways in a dose-dependent manner. This medicinal product is subject to additional monitoring in Australia.

Approved indications

— Treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

Dosing overview

The recommended dose of TEPMETKO is 450 mg (two 225 mg tablets) orally once daily with food. Treatment should continue as long as clinical benefit is observed. Dose adjustment may be required based on individual safety and tolerability, with the recommended dose reduction being 225 mg (one tablet) orally once daily with food.

Key safety warnings

Interstitial lung disease (ILD) or ILD-like adverse reactions have been reported in 8 patients (2.6%) with advanced NSCLC with MET ex14 skipping alterations who received TEPMETKO at the recommended dosage regimen, including 1 case of Grade 3 or higher; serious cases occurred in 4 patients (1.3%), 1 case was fatal. Patients should be monitored for pulmonary symptoms indicative of ILD-like reactions. TEPMETKO should be withheld, and patients should be promptly investigated for alternative diagnosis or specific aetiology of interstitial lung disease. TEPMETKO must be permanently discontinued if interstitial lung disease is confirmed, and the patient be treated accordingly. Increases in ALT and/or AST have been reported in patients with advanced NSCLC harbouring MET ex14 skipping alterations, with a worsening to Grade 3 or higher occurring in 4.9% of patients for ALT and 3.6% of patients for AST. Monitor liver function tests (including ALT, AST and total bilirubin) prior to the start of TEPMETKO, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or bilirubin. TEPMETKO can cause fetal harm when administered to pregnant women. There are no available data on the use of TEPMETKO in pregnant women. However, studies in animals showed malformations (teratogenicity). Women of childbearing potential must use effective contraception during TEPMETKO treatment and for at least 1 week after the last dose. Male patients with female partners of childbearing potential must use barrier contraception during TEPMETKO treatment and for at least 1 week after the last dose.

Contraindications

TEPMETKO is contraindicated in patients with known hypersensitivity to tepotinib or to any of the excipients.

PBS listing

The 225 mg tablet is listed on the PBS with streamlined restriction at an ex-manufacturer price of A$8942.20.

Regulatory history

TEPMETKO received ARTG registration on 17 January 2022. In November 2021, the PBAC deferred its decision regarding TEPMETKO for non-small cell lung cancer. TEPMETKO received provisional approval on 11 January 2022 for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring MET exon 14 skipping alterations. This decision was made based on the overall response rate and duration of response observed in clinical trials, with continued approval dependent on verification in confirmatory trials.