Drug Overview
TEPMETKO, also known as tepotinib, is an oral kinase inhibitor approved for the treatment of patients with metastatic non‑small cell lung cancer (NSCLC). It is the first mesenchymal‑epithelial transition (MET) inhibitor approved by the U.S. Food and Drug Administration (FDA).
Etiology and Symptoms of Non‑Small Cell Lung Cancer
Lung cancer is the most common cancer worldwide, with over 2 million new cases annually. In 2020, the U.S. recorded approximately 228,000 new lung cancer cases and over 135,000 deaths.
Common Symptoms
Early‑stage: Worsening chronic cough, hemoptysis, wheezing, unexplained weight loss, chest pain, dyspnea, decreased appetite, and pulmonary infections (bronchitis, pneumonia).
Advanced‑stage: Bone pain, headache, seizures from brain metastasis, and lymph node masses.
Risk Factors
Risk factors include smoking, secondhand smoke, radiation therapy for other cancers, radon and asbestos exposure, arsenic in drinking water, genetic predisposition, and air pollution.
Epidemiology
NSCLC accounts for about 85% of all lung cancers. MET exon 14 (METex14) skipping mutations are found in 3–5% of NSCLC cases.NSCLC comprises three subtypes: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.
Approval of TEPMETKO (Tepotinib)
U.S. FDA Approval
June 2020: New Drug Application (NDA) submitted to the FDA.
August 2020: Application accepted and granted Priority Review.
February 2021: FDA granted Accelerated Approval for adult patients with metastatic NSCLC harboring METex14 skipping mutations.
Designations: Breakthrough Therapy Designation (BTD) and Orphan Drug Designation (ODD).
Japan Approval
March 2020: Approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for advanced NSCLC with METex14 skipping mutations.
Designations: Sakigake Fast Track Designation and Orphan Drug Designation.
Mechanism of Action of TEPMETKO (Tepotinib)
TEPMETKO is a kinase inhibitor targeting MET, including the METex14 skipping mutation.
Administered once daily, it inhibits MET phosphorylation and subsequent downstream signaling pathways, suppressing tumor growth, anchorage‑independent growth, and migration of MET‑dependent tumor cells.It also inhibits melatonin 2 and imidazoline 1 receptors at clinically relevant concentrations.
Clinical Trials of TEPMETKO (Tepotinib)
FDA approval was based on the pivotal Phase II VISION trial:
Multicenter, non‑randomized, single‑arm, open‑label, multi‑cohort study.
Enrolled 152 patients with advanced or metastatic NSCLC and METex14 skipping alterations (83 previously treated, 69 treatment‑naïve).
Treatment: 450 mg oral tepotinib once daily until disease progression or unacceptable toxicity.
Primary endpoint: Objective Response Rate (ORR) by blinded independent review committee (BIRC).
Secondary endpoint: Duration of Response (DOR).
Efficacy Results
Treatment‑naïve patients: ORR 43%, median DOR 10.8 months.
Previously treated patients: ORR 43%, median DOR 11.1 months.
Common Adverse Reactions
Most common adverse reactions included edema, nausea, fatigue, musculoskeletal pain, diarrhea, and dyspnea.
