About METex14+ mNSCLC | TEPMETKO® (tepotinib)

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Impact of METex14+Testing for METex14+MET
pathway

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Impact of METex14+Testing for METex14+MET
pathway

Starting with a MET inhibitor for patients with METex14+ mNSCLC is critical for maximal benefit.¹

Up to 4% of patients with mNSCLC harbor METex14 skipping alterations²

Real-world studies demonstrated poor outcomes in patients with METex14 skipping who never received a MET inhibitor^1,3,a

^aIn a retrospective analysis using data from 12 institutions, 61 patients with METex14+ NSCLC met the inclusion criteria for survival analysis. Among these 61 patients, 34 never received treatment with a MET TKI.¹

^bOverall survival of 27 patients with stage IV METex14+ NSCLC who received treatment with at least one MET TKI.¹

^cOverall survival of 34 patients with stage IV METex14+ NSCLC who never received a MET TKI.¹

16.5 months

Patients who start with a MET TKI experience a longer OS than those who do not^1,3

What could targeted treatment FIRST mean for your patients?

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Test for METex14+ at diagnosis to help guide treatment decisions¹

MOLECULAR PROFILING

Test for METex14+ upon diagnosis or when a patient presents with metastatic NSCLC. When you test, consider broad molecular profiling that includes MET alterations.¹

TESTING METHODS

METex14+ may be accurately detected through NGS or PCR-based testing. In the VISION trial, METex14+ was identified through either PCR or NGS testing.^4,d

National Comprehensive Cancer Network^® (NCCN^®) recommends⁵:

Clinicians obtain molecular testing results for actionable biomarkers before administering first-line ICI therapy, if clinically feasible
If a METex14+ skipping mutation is discovered during first-line systemic therapy, interrupt current therapy^e and start a MET inhibitor

^dSome patients tested positive using both methodologies.⁴

^eIf there is a good response to current therapy, the NCCN considers it reasonable to continue that therapy.⁵

Impact of METex14+
Testing

Real-world studies demonstrated poor outcomes in patients with METex14 skipping who never received a MET inhibitor^1,3,a

^aIn a retrospective analysis using data from 12 institutions, 61 patients with METex14+ NSCLC met the inclusion criteria for survival analysis. Among these 61 patients, 34 never received treatment with a MET TKI.¹

^bOverall survival of 27 patients with stage IV METex14+ NSCLC who received treatment with at least one MET TKI.¹

^cOverall survival of 34 patients with stage IV METex14+ NSCLC who never received a MET TKI.¹

16.5 months

Patients who start with a MET TKI experience a longer OS than those who do not^1,3

What could targeted treatment FIRST mean for your patients?

Test for METex14+ at diagnosis to help guide treatment decisions¹

MOLECULAR PROFILING

Test for METex14+ upon diagnosis or when a patient presents with metastatic NSCLC. When you test, consider broad molecular profiling that includes MET alterations.¹

TESTING METHODS

METex14+ may be accurately detected through NGS or PCR-based testing. In the VISION trial, METex14+ was identified through either PCR or NGS testing.^4,d

National Comprehensive Cancer Network^® (NCCN^®) recommends⁵:

Clinicians obtain molecular testing results for actionable biomarkers before administering first-line ICI therapy, if clinically feasible
If a METex14+ skipping mutation is discovered during first-line systemic therapy, interrupt current therapy^e and start a MET inhibitor

^dSome patients tested positive using both methodologies.⁴

^eIf there is a good response to current therapy, the NCCN considers it reasonable to continue that therapy.⁵

Dr. Shu on METex14+ identification and treatment considerations

0:44 – Impact of METex14+

2:16 – NCCN Recommendations

Explore efficacy results

INDICATION

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

SUMMARY OF WARNINGS AND PRECAUTIONS

TEPMETKO is associated with the following Warnings and Precautions: interstitial lung disease (ILD)/pneumonitis, hepatotoxicity, pancreatic toxicity, and embryo-fetal toxicity.

Please see additional Important Safety Information at the end of this video and the accompanying full Prescribing Information for TEPMETKO.

Dr Catherine Shu

Hi. My name is Dr Catherine Shu. I'm a thoracic oncologist based out of an academic medical center in New York, New York. I have over 8 years of experience treating patients with MET exon 14 skipping metastatic non-small cell lung cancer.

An estimated 3 to 4% of patients diagnosed with non-small cell lung cancer each year in the United States have MET exon 14 skipping alterations. These patients are associated with a poor prognosis and require a targeted treatment approach.

Approximately 65% of patients with MET exon 14 skipping alterations may be PD-L1 positive, meaning greater than or equal to 1% expression. And these patients have been found to respond poorly to standard of care.

Real-world studies demonstrated positive outcomes in patients with MET exon 14 skipping who received at least one MET TKI.

The Kaplan-Meier Curves shown on this chart demonstrate a difference in median overall survival for patients with stage IV non-small cell lung cancer, harboring MET exon 14 alterations, who received treatment with at least one MET TKI versus patients with MET exon 14 skipping non-small cell lung cancer who never received a MET TKI. Those patients who received a MET TKI had a much longer median overall survival of approximately 2 years, while patients who never received a MET TKI had a median overall survival of approximately 8 months.

Because MET exon 14 skipping is a primary oncogenic driver, it plays an important role in oncogenesis in some cases of non-small cell lung cancer.

NCCN Guidelines strongly recommend that clinicians test for actionable biomarkers in eligible patients with metastatic non-small cell lung cancer. This recommendation can help identify MET exon 14 skipping alterations at diagnosis and inform treatment decisions.

One of the most important parts of diagnosis is to make sure that every lung adenocarcinoma patient gets full next-gen sequencing testing. And that’s so important because we have to be able to test for molecular alterations like MET exon 14. This is because the treatments obviously differ. And the patients with MET exon 14 are different than patients with other alterations.

The NCCN Non-Small Cell Lung Cancer Panel has stratified its preferences for the first-line therapy options for patients with MET exon 14 skipping mutation-positive metastatic non-small cell lung cancer. These are also recommended as subsequent therapy options if the patient was not previously treated with a MET inhibitor.

NCCN also recommends if a MET exon 14 skipping mutation is discovered during the first-line systemic therapy, interrupt the current therapy and start a MET inhibitor, although if there is a good response to current therapy, the NCCN considers it reasonable to continue that therapy.

Tepotinib is an NCCN Category 2A-preferred regimen for first-line and subsequent line setting for patients with MET exon 14 skipping metastatic non-small cell lung cancer.

Please continue watching for Important Safety Information for TEPMETKO.

MET signaling and targeted inhibition

MET pathway signaling⁶

Depending on the cellular context, activated MET signaling may induce processes including cell proliferation, motility, and apoptosis
MET alterations like METex14+ skipping or MET amplification lead to a dysregulation of MET signaling
Dysregulated MET signaling may lead to tumor cell proliferation, migration, and survival

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TEPMETKO MOA⁴

TEPMETKO is an oral inhibitor that targets MET tyrosine kinase activity, including aberrant activity observed with METex14 skipping alterations
In vitro, TEPMETKO inhibits tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent tumor cells

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MET pathway
TEPMETKO mechanism of action

MET pathway signaling⁶

Depending on the cellular context, activated MET signaling may induce processes including cell proliferation, motility, and apoptosis
MET alterations like METex14+ skipping or MET amplification lead to a dysregulation of MET signaling
Dysregulated MET signaling may lead to tumor cell proliferation, migration, and survival

Tap to zoom in

TEPMETKO MOA⁴

TEPMETKO is an oral inhibitor that targets MET tyrosine kinase activity, including aberrant activity observed with METex14 skipping alterations
In vitro, TEPMETKO inhibits tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent tumor cells

Tap to zoom in

“

By identifying these [METex14+] alterations, we can promptly initiate treatment with appropriate targeted therapy.

”

— Razelle Kurzrock, MD, FACP

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AKT=Ak strain transforming; c-Cbl=Casitas B lineage lymphoma; CI=confidence interval; ERK=extracellular signal-regulated kinase; ICI=immune checkpoint inhibitor; JAK=Janus kinase; MET=mesenchymal-epithelial transition; METex14=mesenchymal-epithelial transition exon 14; METex14+=mesenchymal-epithelial transition gene exon 14 skipping alterations; mNSCLC=metastatic non-small cell lung cancer; NCCN=National Comprehensive Cancer Network; NGS=next-generation sequencing; NR=not reached; NSCLC=non-small cell lung cancer; OS=overall survival; PCR=polymerase chain reaction; PI3K=phosphoinositide 3-kinase; RAS=rat sarcoma virus; STAT=signal transducer and activator of transcription; TKI=tyrosine kinase inhibitor.

IMPORTANT SAFETY INFORMATION

TEPMETKO can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold TEPMETKO in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. ILD/pneumonitis occurred in 2% of patients treated with TEPMETKO, with one patient experiencing a Grade 3 or higher event; this event resulted in death.

TEPMETKO can cause hepatotoxicity, which can be fatal. Monitor liver function tests (including alanine aminotransferase [ALT], aspartate aminotransferase [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 total bilirubin. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue TEPMETKO. Increased ALT/increased AST occurred in 18% of patients treated with TEPMETKO. Grade 3 or 4 increased ALT/AST occurred in 4.7% of patients. A fatal adverse reaction of hepatic failure occurred in one patient (0.2%). The median time-to-onset of Grade 3 or higher increased ALT/AST was 47 days (range 1 to 262).

TEPMETKO can cause pancreatic toxicity in the form of elevations in amylase and lipase levels. Increased amylase and/or lipase occurred in 13% of patients, with Grade 3 and 4 increases occurring in 5% and 1.2% of patients, respectively. Monitor amylase and lipase levels at baseline and regularly during treatment with TEPMETKO and temporarily withhold, dose reduce, or permanently discontinue based on severity of the adverse event.

TEPMETKO can cause embryo-fetal toxicity. Based on findings in animal studies and its mechanism of action, TEPMETKO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential or males with female partners of reproductive potential to use effective contraception during treatment with TEPMETKO and for one week after the last dose.

Avoid concomitant use of TEPMETKO with certain P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

Fatal adverse reactions occurred in one patient (0.3%) due to pneumonitis, one patient (0.3%) due to hepatic failure, one patient (0.3%) due to dyspnea from fluid overload, one patient (0.3%) due to pneumonia, one patient (0.3%) due to sepsis, and one patient (0.3%) from unknown cause.

Serious adverse reactions occurred in 51% of patients who received TEPMETKO. Serious adverse reactions in >2% of patients included pleural effusion (6%), pneumonia (6%), edema (5%), general health deterioration (3.8%), dyspnea (3.5%), musculoskeletal pain (2.9%), and pulmonary embolism (2.2%).

The most common adverse reactions (≥20%) in patients who received TEPMETKO were edema (81%), nausea (31%), fatigue (30%), musculoskeletal pain (30%), diarrhea (29%), dyspnea (24%), rash (21%), and decreased appetite (21%).

Clinically relevant adverse reactions in <10% of patients who received TEPMETKO included ILD/pneumonitis, fever, dizziness, pruritus, and headache.

Selected laboratory abnormalities (≥20%) from baseline in patients receiving TEPMETKO in descending order were: decreased albumin (81%), increased creatinine (60%), decreased lymphocytes (57%), increased alkaline phosphatase (ALP) (52%), increased ALT (50%), increased AST (40%), decreased sodium (36%), decreased hemoglobin (31%), increased gamma-glutamyltransferase (GGT) (29%), increased potassium (26%), increased amylase (25%), decreased leukocytes (25%), decreased platelets (24%), and increased lipase (21%).

The most common Grade 3-4 laboratory abnormalities (≥2%) in descending order were: decreased lymphocytes (15%), decreased albumin (9%), decreased sodium (9%), increased GGT (6%), increased amylase (5%), increased lipase (5%), increased ALT (4.9%), increased AST (3.6%), and decreased hemoglobin (3.6%).

INDICATION

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

Please see the full Prescribing Information for TEPMETKO.

Reference: 1. TEPMETKO. Prescribing information. EMD Serono, Inc.

References: 1. TEPMETKO. Prescribing information. EMD Serono, Inc. 2. Mazieres J, Paik PK, Garassino MC, et al. Tepotinib treatment in patients with MET exon 14–skipping non–small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial. JAMA Oncol. 2023;9(9):1260-1266. 3. Data on file. EMD Serono, Inc., Boston, MA. 4. Smit EF, Garassino MC, Felip E, et al. Tepotinib outcomes according to prior therapies in patients with MET exon 14 (METex14) skipping NSCLC. Poster presented at: European Society for Medical Oncology (ESMO) congress; September 9-13, 2022; Paris, France. Poster 985P. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed May 8, 2026. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

References: 1. TEPMETKO. Prescribing information. EMD Serono, Inc. 2. 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. 3. Mazieres J, Paik PK, Garassino MC, et al. Tepotinib treatment in patients with MET exon 14–skipping non–small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial. JAMA Oncol. 2023;9(9):1260-1266.

References: 1. TEPMETKO. Prescribing information. EMD Serono, Inc. 2. 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. 3. Data on file. EMD Serono, Inc., Boston, MA. 4. Mazieres J, Paik PK, Garassino MC, et al. Tepotinib treatment in patients with MET exon 14-skipping non-small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial. JAMA Oncol. 2023;9(9):1260-1266.

References: 1. Awad MM, Leonardi GC, Kravets S, et al. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis. Lung Cancer. 2019;133:96-102. 2. Salgia R. MET in lung cancer: biomarker selection based on scientific rationale. Mol Cancer Ther. 2017;16(4):555-565. 3. Asad Zadeh Vosta Kolaei F, Cai B, Kanakamedala H, et al. Biomarker testing patterns and treatment outcomes in patients with advanced non-small cell lung cancer and MET exon 14 skipping mutations: a descriptive analysis from the US. Front Oncol. 2022;12:786124. 4. TEPMETKO. Prescribing information. EMD Serono, Inc. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed May 8, 2026. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 6. Paik PK, Iams WT, Husain H, O'Hara RM Jr, Adewusi E, Le X. Tepotinib in patients with MET exon 14 skipping non-small cell lung cancer. Cancer Treat Rev. 2025;139:102990.

References: 1. TEPMETKO. Prescribing information. EMD Serono, Inc. 2. Mazieres J, Paik PK, Garassino MC, et al. Tepotinib treatment in patients with MET exon 14-skipping non-small cell lung cancer: long-term follow-up of the VISION phase 2 nonrandomized clinical trial. JAMA Oncol. 2023;9(9):1260-1266. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.5.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed May 8, 2026. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. Salgia R. MET in lung cancer: biomarker selection based on scientific rationale. Mol Cancer Ther. 2017;16(4):555-565. 5. Awad MM, Leonardi GC, Kravets S, et al. Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: a retrospective analysis. Lung Cancer. 2019;133:96-102. 6. Asad Zadeh Vosta Kolaei F, Cai B, Kanakamedala H, et al. Biomarker testing patterns and treatment outcomes in patients with advanced non-small cell lung cancer and MET exon 14 skipping mutations: a descriptive analysis from the US. Front Oncol. 2022;12:786124. 7. Sabari JK, Leonardi GC, Shu CA, et al. PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers. Ann Oncol. 2018;29(10):2085-2091. 8. 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.

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