TEPMETKO: Uses, Dosage & Side Effects
A selective MET inhibitor for the treatment of advanced non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations
TEPMETKO (tepotinib) is a prescription oral medication used to treat adults with advanced or metastatic non-small cell lung cancer (NSCLC) that harbors mesenchymal-epithelial transition factor (MET) exon 14 skipping mutations. Tepotinib is a highly selective, potent inhibitor of the MET receptor tyrosine kinase. It is taken as two 225 mg tablets (450 mg total) once daily with food. In the pivotal VISION clinical trial, TEPMETKO demonstrated a durable objective response rate in treatment-naïve and previously treated patients with MET exon 14 skipping NSCLC. The most common side effects include edema, nausea, diarrhea, and elevated blood creatinine. TEPMETKO is manufactured by Merck Healthcare KGaA and is approved in the EU, US, Japan, and several other countries.
Quick Facts: TEPMETKO
Key Takeaways
- TEPMETKO (tepotinib) is a highly selective MET inhibitor specifically developed for advanced non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations, a genomic alteration found in approximately 3–4% of NSCLC cases.
- The recommended dose is 450 mg (two 225 mg tablets) taken orally once daily with food. Treatment continues as long as the patient derives clinical benefit and can tolerate the side effects.
- In the pivotal VISION trial, TEPMETKO demonstrated an objective response rate of approximately 46–56% in patients with MET exon 14 skipping NSCLC, with durable responses lasting a median of 11 months or longer.
- Key side effects to monitor include interstitial lung disease (ILD), which requires immediate medical attention, as well as peripheral edema, gastrointestinal symptoms, hepatotoxicity, and QT prolongation.
- TEPMETKO interacts with several medications through inhibition of drug transporters (P-gp, BCRP, MATE1/2-K, OATP1B), potentially increasing levels of dabigatran, digoxin, metformin, rosuvastatin, and others.
What Is TEPMETKO and What Is It Used For?
TEPMETKO contains the active substance tepotinib, a highly selective, oral, small-molecule inhibitor of the mesenchymal-epithelial transition factor (MET) receptor tyrosine kinase. MET is a transmembrane receptor that is normally activated by its ligand, hepatocyte growth factor (HGF), triggering intracellular signaling pathways that regulate cell growth, survival, motility, and invasion. Under normal physiological conditions, MET signaling is tightly regulated and plays important roles in embryonic development, organ regeneration, and wound healing. However, when MET becomes aberrantly activated through genetic mutations, gene amplification, or protein overexpression, it can drive the development and progression of various cancers, including non-small cell lung cancer (NSCLC).
One of the most clinically significant MET alterations in NSCLC is the MET exon 14 skipping mutation. Exon 14 of the MET gene encodes a portion of the intracellular juxtamembrane domain that contains a critical ubiquitination site. Under normal conditions, this site serves as a signal for the cell’s protein degradation machinery (the ubiquitin-proteasome pathway) to break down the MET receptor after it has been activated, thereby terminating its signaling activity. When exon 14 is “skipped” due to mutations that disrupt normal RNA splicing, the resulting MET protein lacks this degradation signal. Consequently, the MET receptor accumulates on the cell surface and remains constitutively active, continuously stimulating downstream oncogenic signaling pathways including the RAS/RAF/MAPK and PI3K/AKT cascades. This uncontrolled signaling promotes tumor cell proliferation, survival, and metastasis.
MET exon 14 skipping mutations are found in approximately 3–4% of all NSCLC cases, making it a relatively rare but clinically actionable molecular subtype. These mutations are more commonly observed in older patients (median age approximately 73 years), in adenocarcinoma and sarcomatoid histologies, and in patients who have never smoked or are former smokers. Despite its relative rarity, MET exon 14 skipping NSCLC represents a significant unmet medical need because these tumors often respond poorly to standard chemotherapy and immunotherapy, and patients with this molecular subtype tend to have a poor prognosis without targeted treatment.
Tepotinib works by binding to the ATP-binding site of the MET receptor kinase domain with high selectivity and potency (IC50 of approximately 3 nM). By occupying this binding site, tepotinib blocks the phosphorylation of MET and prevents the activation of downstream signaling cascades that drive tumor growth. In preclinical studies, tepotinib demonstrated potent anti-tumor activity in cell lines and xenograft models harboring MET exon 14 skipping mutations, MET amplification, and MET overexpression. Its high selectivity for MET over other kinases contributes to a favorable tolerability profile compared with less selective multi-kinase inhibitors.
The clinical efficacy of TEPMETKO was primarily established in the VISION trial (NCT02864992), a pivotal, open-label, multicenter, single-arm phase II study that enrolled patients with advanced or metastatic NSCLC harboring MET exon 14 skipping mutations as identified by liquid biopsy (circulating tumor DNA) or tissue biopsy. The VISION trial included both treatment-naïve patients (who had not received prior systemic therapy for advanced disease) and previously treated patients (who had progressed on one or two prior lines of therapy, including platinum-based chemotherapy and/or immunotherapy).
Key efficacy results from the VISION trial demonstrated:
- Overall objective response rate (ORR): Approximately 46% by independent review committee (IRC) assessment across the overall population, with ORR reaching up to 56% in treatment-naïve patients.
- Median duration of response (DoR): Approximately 11.1 months by IRC, indicating durable responses in responding patients.
- Median progression-free survival (PFS): Approximately 8.5–11 months depending on the patient subgroup and assessment method.
- Intracranial activity: TEPMETKO demonstrated activity in patients with brain metastases, an important consideration given the propensity of NSCLC to metastasize to the central nervous system.
TEPMETKO received its first approval in Japan in March 2020, followed by conditional approval by the European Medicines Agency (EMA) and accelerated approval by the U.S. Food and Drug Administration (FDA) in February 2021. It has since been approved in additional countries worldwide. TEPMETKO is classified as an orphan drug in the EU given the rarity of the target population. Its approval marked a significant milestone in precision oncology for lung cancer, providing a targeted oral therapy for a molecularly defined subset of patients who previously had limited treatment options.
Before starting TEPMETKO, your doctor must confirm that your cancer cells harbor a MET exon 14 skipping mutation through a validated molecular diagnostic test, either using a tissue biopsy sample or a liquid biopsy (blood test for circulating tumor DNA). Comprehensive genomic profiling that includes MET exon 14 skipping analysis is recommended for all patients with advanced NSCLC, as identification of this mutation opens the door to targeted therapy with TEPMETKO that can significantly improve outcomes compared with standard chemotherapy.
What Should You Know Before Taking TEPMETKO?
Contraindications
The only absolute contraindication to TEPMETKO is hypersensitivity (allergy) to tepotinib or to any of the other ingredients in the formulation. The excipients in TEPMETKO tablets include mannitol, colloidal anhydrous silica, crospovidone, magnesium stearate, and microcrystalline cellulose in the tablet core, and hypromellose, lactose monohydrate, macrogol, triacetin, red iron oxide (E172), and titanium dioxide (E171) in the film coating. Patients with known hypersensitivity to any of these substances should not take TEPMETKO.
TEPMETKO contains 4.4 mg of lactose monohydrate per tablet (8.8 mg per daily dose of two tablets). Patients with rare hereditary conditions of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should consult their doctor before taking this medicine.
Warnings and Precautions
TEPMETKO can cause interstitial lung disease (ILD), also known as pneumonitis, which can be severe or fatal. Tell your doctor immediately if you develop new or worsening respiratory symptoms including shortness of breath, cough, or fever. Your doctor may need to interrupt, reduce, or permanently discontinue TEPMETKO treatment.
Before and during treatment with TEPMETKO, your doctor should be informed about the following conditions and will monitor you accordingly:
- Lung and breathing problems (ILD/Pneumonitis): TEPMETKO can cause interstitial lung disease, a potentially serious condition characterized by inflammation and scarring of the lung tissue. ILD occurred in approximately 5–7% of patients in clinical trials. Symptoms include sudden onset or worsening of shortness of breath, non-productive cough, and fever. Your doctor will monitor you for respiratory symptoms throughout treatment. If ILD is suspected, TEPMETKO will be withheld pending investigation. If ILD is confirmed, TEPMETKO must be permanently discontinued.
- Liver function: TEPMETKO can cause elevated liver enzymes (ALT, AST, alkaline phosphatase), indicating potential hepatotoxicity. Your doctor will perform blood tests to check liver function before starting treatment and periodically during treatment. Dose adjustments or treatment discontinuation may be required if significant liver enzyme elevations occur.
- Heart rhythm (QT prolongation): TEPMETKO may cause prolongation of the QT interval on electrocardiogram (ECG), which can increase the risk of abnormal heart rhythms. Your doctor may perform ECG monitoring during treatment, particularly if you have pre-existing heart conditions, electrolyte imbalances, or are taking other medications known to prolong the QT interval.
- Fluid retention (edema): Peripheral edema (swelling of the legs, feet, ankles, or other body areas) is one of the most common side effects of TEPMETKO. Your doctor should monitor for signs of significant fluid accumulation and may initiate diuretic therapy or adjust the TEPMETKO dose if needed.
Children and Adolescents
TEPMETKO has not been studied in children and adolescents under 18 years of age. The safety and efficacy of tepotinib have not been established in this population, and it is not recommended for use in pediatric patients. MET exon 14 skipping mutations are extremely rare in pediatric lung cancers.
Pregnancy and Breastfeeding
TEPMETKO must not be used during pregnancy unless your doctor has determined that the potential benefit clearly outweighs the risk to the unborn baby. Based on its mechanism of action as a kinase inhibitor and findings from animal studies, tepotinib may cause harm to a developing fetus. A pregnancy test is recommended before starting TEPMETKO treatment.
Contraception for women: Women of childbearing potential must use effective contraception during treatment with TEPMETKO and for at least 1 week after the last dose. If you are taking hormonal contraceptives (such as the pill), you must also use an additional barrier method (such as condoms) during treatment, as tepotinib may reduce the effectiveness of hormonal contraceptives through drug transporter interactions.
Contraception for men: Male patients should use a barrier method of contraception to prevent their partner from becoming pregnant during treatment with TEPMETKO and for at least 1 week after the last dose.
Breastfeeding: It is not known whether tepotinib or its metabolites are excreted in human breast milk. A risk to the breastfed child cannot be excluded. You must stop breastfeeding during treatment with TEPMETKO and for at least 1 week after the last dose.
Driving and Operating Machinery
TEPMETKO has no known effect on the ability to drive or operate machinery. Based on clinical trial data, tepotinib is not expected to impair these abilities. However, if you experience any adverse effects such as fatigue or dizziness that could affect your concentration or reaction time, refrain from driving or using machines until you feel well again.
How Does TEPMETKO Interact with Other Drugs?
Understanding drug interactions is particularly important for patients taking TEPMETKO, as tepotinib inhibits several membrane drug transporters that influence the absorption, distribution, and elimination of many commonly prescribed medications. Unlike some other kinase inhibitors that primarily interact through cytochrome P450 (CYP) enzyme inhibition, the principal drug interactions of tepotinib are mediated through its effects on drug transporter proteins.
Tepotinib itself is metabolized primarily by CYP3A4 and CYP2C8 enzymes. It is also a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). While strong CYP3A4 inhibitors or inducers may theoretically affect tepotinib exposure, the clinical significance of such interactions has not been fully characterized, and no formal dose adjustment recommendations have been made based on concomitant CYP3A4 modulators.
The clinically significant drug interactions of TEPMETKO are primarily driven by its inhibition of the following drug transporters:
- P-glycoprotein (P-gp): Tepotinib inhibits P-gp, which can increase blood levels of P-gp substrate drugs.
- Breast Cancer Resistance Protein (BCRP): Inhibition of BCRP by tepotinib can increase absorption and systemic exposure of BCRP substrates.
- MATE1 and MATE2-K: Tepotinib inhibits these renal transporters, which can reduce the kidney excretion of substrate drugs such as metformin.
- OATP1B1 and OATP1B3: Inhibition of these hepatic uptake transporters can increase blood levels of statin drugs and other OATP substrates.
Clinically Significant Interactions
| Interacting Drug | Therapeutic Use | Mechanism | Clinical Consequence |
|---|---|---|---|
| Dabigatran | Prevention of stroke and blood clots | P-gp inhibition | Increased dabigatran levels; higher bleeding risk |
| Digoxin | Irregular heartbeat and heart failure | P-gp inhibition | Increased digoxin levels; risk of toxicity |
| Aliskiren | High blood pressure | P-gp inhibition | Increased aliskiren exposure |
| Everolimus | Cancer treatment, organ transplant rejection | P-gp inhibition | Increased everolimus levels; enhanced toxicity |
| Sirolimus | Prevention of organ transplant rejection | P-gp inhibition | Increased sirolimus levels |
| Rosuvastatin | High cholesterol | BCRP and OATP1B inhibition | Increased rosuvastatin levels; muscle toxicity risk |
| Methotrexate | Cancer, inflammatory diseases | BCRP and OATP1B inhibition | Increased methotrexate levels; enhanced toxicity |
| Topotecan | Cancer treatment | BCRP and P-gp inhibition | Increased topotecan levels; myelosuppression risk |
| Metformin | Type 2 diabetes | MATE1/MATE2-K inhibition | Reduced renal clearance of metformin; lactic acidosis risk |
If you are currently taking any of the medications listed above, or any other prescription or over-the-counter medications, herbal supplements, or vitamins, inform your doctor before starting TEPMETKO. Your doctor may need to adjust the doses of your other medications, increase monitoring (for example, more frequent blood tests or ECG monitoring), or consider alternative treatments.
It is especially important to inform your doctor if you are taking dabigatran or other direct oral anticoagulants, as the increased bleeding risk associated with elevated dabigatran levels can be clinically significant. Similarly, digoxin has a narrow therapeutic window, and even modest increases in digoxin levels can lead to toxicity symptoms including nausea, vomiting, visual disturbances, and cardiac arrhythmias. Metformin accumulation due to MATE1/2-K inhibition can increase the risk of lactic acidosis, a rare but potentially life-threatening metabolic complication.
Always carry an up-to-date list of all medications you are taking, including prescription drugs, over-the-counter medicines, herbal products, and dietary supplements. Share this list with every healthcare provider you see. Do not start or stop any medication without discussing it with your oncologist first, as changes to your medication regimen could affect the safety and efficacy of TEPMETKO treatment.
What Is the Correct Dosage of TEPMETKO?
TEPMETKO should always be taken exactly as your doctor has prescribed. Do not change your dose or stop taking TEPMETKO without consulting your oncologist first. The standard dosing regimen has been established through clinical trials to provide optimal drug exposure while maintaining an acceptable safety profile.
Adults
| Parameter | Recommendation |
|---|---|
| Standard dose | 450 mg (two 225 mg tablets) once daily |
| Reduced dose | 225 mg (one 225 mg tablet) once daily |
| Administration | Take with food or shortly after a meal |
| How to take | Swallow tablets whole; do not chew |
| Duration of treatment | Continue as long as clinical benefit is observed |
Taking TEPMETKO with food is important because food significantly increases the absorption of tepotinib, ensuring that the full therapeutic dose reaches the bloodstream. In pharmacokinetic studies, administration with a high-fat, high-calorie meal increased tepotinib exposure compared with the fasted state. Swallowing the tablets whole ensures consistent drug release and absorption.
If you have difficulty swallowing: TEPMETKO tablets can be dispersed in water for patients who cannot swallow whole tablets. Place both tablets in a glass (without crushing them), add 30 mL (approximately two tablespoons) of plain non-carbonated water – do not use other liquids – and stir until the tablets disintegrate into very small pieces. This may take a few minutes; the tablets will not dissolve completely. Drink the mixture within one hour. Rinse the glass thoroughly with an additional 30 mL of water and drink immediately to ensure you have taken the complete dose.
Nasogastric tube administration: For patients with a nasogastric tube of size 8 French or larger, the same water dispersion method can be used. Prepare the mixture as described above in 30 mL of non-carbonated water, administer through the tube within 1 hour, and flush the glass and syringe twice with 30 mL each to ensure complete dose delivery.
Your doctor may reduce the dose from 450 mg to 225 mg once daily to manage certain side effects. If the 225 mg dose is still not tolerated, your doctor may temporarily interrupt treatment for a few days before restarting. Dose re-escalation to 450 mg may be considered once the side effect has resolved or improved to an acceptable level.
Children and Adolescents
TEPMETKO has not been studied in patients under 18 years of age. No dosing recommendations can be made for pediatric patients. MET exon 14 skipping mutations in NSCLC are almost exclusively observed in adult patients.
Elderly Patients
No dose adjustment is required for elderly patients. In the VISION trial, the median age of enrolled patients was approximately 73 years, reflecting the typical demographics of MET exon 14 skipping NSCLC. The safety and efficacy profiles in older patients were consistent with those observed in the overall study population. However, elderly patients may be more susceptible to certain side effects such as edema and may require closer monitoring.
Missed Dose
If you forget to take a dose of TEPMETKO, take it as soon as you remember. However, if your next scheduled dose is due within 8 hours, skip the missed dose and take your next dose at the usual time. Do not take a double dose to make up for a forgotten dose. If you are unsure about what to do, contact your doctor or pharmacist for advice.
Overdose
Experience with overdose of TEPMETKO is limited. The symptoms of overdose are expected to be consistent with the known side effects described in the side effects section. If you suspect an overdose, contact your doctor immediately or go to the nearest emergency department. Treatment is supportive, with monitoring of symptoms and vital signs. There is no specific antidote for tepotinib.
What Are the Side Effects of TEPMETKO?
Like all medicines, TEPMETKO can cause side effects, although not everybody gets them. It is important to be aware of the potential side effects so that you can recognize them early and inform your doctor promptly. Some side effects can be serious and require immediate medical attention, while others may be managed with supportive care or dose adjustments.
Your oncology team will monitor you regularly during treatment with blood tests, physical examinations, and imaging studies to detect side effects early. Open communication with your healthcare team about any new or changing symptoms is essential for safe treatment with TEPMETKO.
Serious Side Effects – Seek Immediate Medical Attention
Tell your doctor immediately if you develop new or worsening symptoms such as sudden shortness of breath, persistent cough, or fever. These may be signs of interstitial lung disease, a serious condition that requires immediate medical evaluation and treatment. ILD is common (may affect up to 1 in 10 patients) and can be fatal if not promptly recognized and managed. Your doctor will withhold TEPMETKO and perform imaging studies if ILD is suspected.
Side Effect Frequency Overview
Very Common
May affect more than 1 in 10 people
- Edema (swelling caused by fluid accumulation in the body, including peripheral edema of legs, ankles, feet, and generalized fluid retention)
- Nausea
- Vomiting
- Diarrhea
- Elevated blood creatinine levels (a marker of potential kidney function changes)
- Elevated liver enzymes – alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (indicating potential liver stress)
- Elevated amylase and lipase levels (enzymes associated with pancreatic function; may indicate potential digestive system effects)
- Decreased blood albumin (hypoalbuminemia, a protein important for maintaining fluid balance)
Common
May affect up to 1 in 10 people
- Interstitial lung disease (ILD) / pneumonitis – inflammation of the lung tissue causing breathing difficulties
- QT prolongation (changes in the heart’s electrical activity visible on ECG, which may increase the risk of abnormal heart rhythms)
Understanding Key Side Effects in Detail
Peripheral edema is the most frequently reported side effect of TEPMETKO, occurring in a significant proportion of patients. It typically manifests as swelling of the lower extremities (legs, ankles, and feet) but can also involve the hands, arms, or face. The edema is thought to be related to MET inhibition in normal tissues and alterations in vascular permeability. Management may include elevation of the affected limbs, compression stockings, dietary sodium restriction, and diuretic medications. In some cases, dose reduction or treatment interruption may be necessary for severe or symptomatic edema.
Gastrointestinal effects including nausea, vomiting, and diarrhea are common but typically mild to moderate in severity. These symptoms can usually be managed with antiemetic medications (for nausea and vomiting), antidiarrheal agents, and dietary modifications such as eating smaller, more frequent meals and avoiding spicy or fatty foods. Staying well hydrated is important, particularly if you experience diarrhea or vomiting.
Elevated blood creatinine is frequently observed during TEPMETKO treatment. It is important to note that tepotinib inhibits renal tubular creatinine secretion (through MATE1/2-K and OCT2 transporter inhibition), leading to increases in serum creatinine that do not necessarily reflect true kidney injury. Your doctor will interpret creatinine changes in the context of other kidney function markers to determine whether the elevation represents a drug effect on creatinine transport or actual kidney impairment.
Liver enzyme elevations (increased ALT, AST, and alkaline phosphatase) occur in a substantial proportion of patients. Most elevations are mild to moderate and asymptomatic, but they require regular monitoring through blood tests. Significant elevations may require dose modification or treatment discontinuation. Tell your doctor if you develop symptoms suggestive of liver problems, such as yellowing of the skin or eyes (jaundice), dark urine, unusual fatigue, or abdominal pain.
QT prolongation is a change in the heart’s electrical conduction that can be detected on ECG. While most cases are asymptomatic, significant QT prolongation can predispose to dangerous heart rhythm disturbances. Your doctor may perform periodic ECG monitoring, particularly during the initial weeks of treatment, if you have risk factors for QT prolongation, or if you are taking other medications that can affect the QT interval.
It is important to report any suspected side effects to your doctor or pharmacist, even if they are not listed here. You can also report side effects directly to your national pharmacovigilance authority. Reporting helps to continuously monitor the benefit-risk balance of TEPMETKO and can lead to important safety updates.
How Should You Store TEPMETKO?
Proper storage of TEPMETKO is essential to ensure that the medication remains effective and safe throughout its shelf life. TEPMETKO film-coated tablets do not require any special storage conditions and can be kept at room temperature.
Follow these storage guidelines:
- Temperature: No special temperature storage requirements. Store at normal room temperature.
- Packaging: Keep the tablets in the original transparent blister packaging (consisting of a multi-layer form foil and an aluminum lid) until you are ready to take them. This protects the tablets from moisture and light.
- Expiry date: Do not use TEPMETKO after the expiry date (EXP) printed on the carton and blister pack. The expiry date refers to the last day of the stated month.
- Accessibility: Keep this medicine out of the sight and reach of children.
- Disposal: Do not dispose of unused medicines in wastewater or household waste. Ask your pharmacist about how to properly dispose of medicines you no longer use. These measures help protect the environment.
TEPMETKO tablets are white-pink, oval, biconvex, approximately 18 × 9 mm in size, and embossed with “M” on one side and plain on the other. Each pack contains 60 tablets. If you notice any change in the appearance of your tablets (discoloration, crumbling, or unusual odor), do not take them and consult your pharmacist.
What Does TEPMETKO Contain?
Understanding the composition of your medication can help you identify potential allergens or intolerances. Below is a detailed breakdown of the ingredients in TEPMETKO tablets:
Active Ingredient
The active substance is tepotinib. Each film-coated tablet contains 225 mg of tepotinib, present in the tablet as tepotinib hydrochloride hydrate. Tepotinib is a selective inhibitor of the MET (mesenchymal-epithelial transition factor) receptor tyrosine kinase.
Inactive Ingredients (Excipients)
Tablet core:
- Mannitol – a sugar alcohol used as a filler and diluent
- Colloidal anhydrous silica – a flow agent that improves tablet manufacturing
- Crospovidone – a disintegrant that helps the tablet break apart for absorption
- Magnesium stearate – a lubricant used in tablet compression
- Microcrystalline cellulose – a filler and binder derived from plant fiber
Film coating:
- Hypromellose – a coating polymer that provides a smooth finish
- Lactose monohydrate (4.4 mg per tablet) – a milk-derived sugar used as a filler in the coating
- Macrogol (polyethylene glycol) – a plasticizer for the coating
- Triacetin – a plasticizer that improves coating flexibility
- Red iron oxide (E172) – a coloring agent that gives the tablet its white-pink appearance
- Titanium dioxide (E171) – a whitening and opacifying agent
TEPMETKO contains 4.4 mg of lactose monohydrate per tablet (8.8 mg per daily dose of two tablets). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. The amount of lactose in TEPMETKO is very small and is unlikely to cause problems for most lactose-intolerant patients, but you should discuss this with your healthcare provider.
Frequently Asked Questions About TEPMETKO
MET exon 14 skipping is a specific genetic alteration in the MET gene that prevents normal degradation of the MET receptor protein. This results in continuous activation of growth signals that drive cancer. It is found in approximately 3–4% of non-small cell lung cancers and is more common in older patients, adenocarcinomas, and sarcomatoid carcinomas. The mutation can be detected through molecular diagnostic tests using either a tissue biopsy (collected from a tumor sample) or a liquid biopsy (a blood test that detects circulating tumor DNA). Your oncologist will order appropriate testing if MET exon 14 skipping is suspected.
In the VISION clinical trial, the median time to initial response was approximately 1.8 months (about 8 weeks) from the start of treatment. However, individual responses may vary. Some patients experienced tumor shrinkage within the first few weeks, while others took longer to show a measurable response. Your oncologist will typically order imaging scans (such as CT scans) every 6–8 weeks to assess how well the treatment is working. It is important to continue taking TEPMETKO as prescribed, even before your first imaging assessment.
Yes, TEPMETKO should be taken with food or shortly after a meal. Taking the tablets with food improves the absorption of tepotinib into the bloodstream, ensuring you receive the full therapeutic benefit of the medication. There are no specific dietary restrictions, but taking the tablets consistently with meals at approximately the same time each day helps maintain steady drug levels. Swallow the tablets whole with water; do not chew or crush them.
Peripheral edema (swelling of the legs, ankles, feet, or other body parts) is one of the most common side effects of TEPMETKO. If you notice new or worsening swelling, inform your oncologist at your next appointment. Mild edema may be managed with leg elevation, compression stockings, reduced dietary salt intake, and staying active. Your doctor may prescribe diuretic (water) tablets to help remove excess fluid. For moderate to severe edema, your doctor may reduce the TEPMETKO dose from 450 mg to 225 mg daily or temporarily pause treatment. Do not stop taking TEPMETKO without consulting your doctor.
No, TEPMETKO is a targeted therapy, which is different from both chemotherapy and immunotherapy. Chemotherapy works by killing rapidly dividing cells (both cancer and normal cells), causing widespread side effects. Immunotherapy works by activating the immune system to recognize and attack cancer cells. TEPMETKO, in contrast, is a precision medicine that specifically targets the MET receptor tyrosine kinase – an abnormal protein that drives cancer growth in tumors with MET exon 14 skipping mutations. Because it is highly selective for MET, TEPMETKO generally has a different and often more tolerable side effect profile than chemotherapy.
In the pivotal VISION trial, TEPMETKO achieved an overall objective response rate of approximately 46–56% in patients with MET exon 14 skipping NSCLC, meaning that about half of patients experienced significant tumor shrinkage. The median duration of response was approximately 11 months, indicating durable benefit in responding patients. Median progression-free survival ranged from approximately 8.5 to 11 months. These results are considered clinically meaningful for this patient population, which historically had limited effective treatment options. However, individual outcomes vary, and your oncologist can discuss what these results may mean for your specific situation.
References
- European Medicines Agency (EMA). TEPMETKO – Summary of Product Characteristics. Last updated 2024. Available from: www.ema.europa.eu/en/medicines/human/EPAR/tepmetko
- U.S. Food and Drug Administration (FDA). TEPMETKO (tepotinib) Prescribing Information. Approved February 2021, last revised 2024.
- Paik PK, Felip E, Veillon R, et al. Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020;383(10):931–943. doi:10.1056/NEJMoa2004407
- Le X, Sakai H, Felip E, et al. Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice. Clin Cancer Res. 2022;28(6):1117–1126.
- Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(9):869–885.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2024.
- World Health Organization (WHO). WHO Model List of Essential Medicines, 23rd List. Geneva: World Health Organization; 2023.
- Drilon A, Clark JW, Weiss J, et al. Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration. Nat Med. 2020;26(1):47–51.
- Recondo G, Che J, Janne PA, Awad MM. Targeting MET Dysregulation in Cancer. Cancer Discov. 2020;10(7):922–934.
- British National Formulary (BNF). Tepotinib. National Institute for Health and Care Excellence (NICE). Accessed January 2026.
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