TEPMETKO® Safety Profile for HCPs

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Safety & Tolerability AE Management

The safety and tolerability of TEPMETKO were established in 313 patients¹

Most adverse reactions observed in the VISION trial were mild to moderate (Grade 1 or 2)¹

ARs in ≥10% of patients with mNSCLC harboring METex14+^a

Fatal adverse reactions occurred in 1.9% of patients who received TEPMETKO, including pneumonitis (0.3%), hepatic failure (0.3%), dyspnea from fluid overload (0.3%), pneumonia (0.3%), sepsis (0.3%), and death of unknown cause (0.3%)¹
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%)¹

See additional safety information in the next tab.

^aSeverity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.¹
^bEdema includes eye edema, face edema, generalized edema, localized edema, edema, genital edema, peripheral edema, peripheral swelling, periorbital edema, and scrotal edema.¹
^cFatigue includes asthenia and fatigue.¹
^dAbdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain, and hepatic pain.¹
^eVomiting includes retching and vomiting.¹
^fMusculoskeletal pain includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, non-cardiac chest pain, pain in extremity, and spinal pain.¹
^gDyspnea includes dyspnea, dyspnea at rest, and dyspnea exertional.¹
^hCough includes cough and productive cough.¹
ⁱRash includes rash, palmar-plantar erythrodysesthesia syndrome, rash maculo-papular, eczema, exfoliative rash, rash erythematous, rash pustular, skin exfoliation, dermatitis acneiform, drug eruption, dermatitis, rash pruritic, dermatitis bullous, toxic skin eruption.¹
^jPneumonia includes pneumonia, pneumonia aspiration, and pneumonia bacterial.¹

Laboratory abnormalities^1,a,k

Selected laboratory abnormalities (≥20%) from baseline in patients receiving TEPMETKO in descending order were: decreased albumin (81%), increased creatinine (60%), decreased lymphocytes (57%), increased ALP (52%), increased ALT (50%), increased AST (40%), decreased sodium (36%), decreased hemoglobin (31%), increased 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%)

Treatment modifications due to an AR in patients who received TEPMETKO¹

Dosage interruptions (53%): ARs which required dosage interruption in >2% of patients who received TEPMETKO included edema (28%), increased blood creatinine (6%), pleural effusion (3.5%), nausea (3.2%), increased ALT (2.9%), pneumonia (2.6%), decreased appetite (2.2%), and dyspnea (2.2%)
Dose reductions (36%): ARs which required dose reductions in >2% of patients who received TEPMETKO included edema (22%), increased blood creatinine (2.9%), fatigue (2.2%), and pleural effusion (2.2%)
Permanent discontinuation (25%): The most frequent adverse reactions (>1%) leading to permanent discontinuations of TEPMETKO were edema (8%), pleural effusion (1.6%), and general health deterioration (1.6%)

^aSeverity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.¹
^kThe denominator used to calculate the rate varied from 268 to 309 based on the number of patients with a baseline value and at least one posttreatment value.¹

Adverse Reactions
Additional Safety Information

Most adverse reactions observed in the VISION trial were mild to moderate (Grade 1 or 2)¹

ARs in ≥10% of patients with mNSCLC harboring METex14+^a

Fatal adverse reactions occurred in 1.9% of patients who received TEPMETKO, including pneumonitis (0.3%), hepatic failure (0.3%), dyspnea from fluid overload (0.3%), pneumonia (0.3%), sepsis (0.3%), and death of unknown cause (0.3%)¹
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%)¹

See additional safety information in the next tab.

^aSeverity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.¹
^bEdema includes eye edema, face edema, generalized edema, localized edema, edema, genital edema, peripheral edema, peripheral swelling, periorbital edema, and scrotal edema.¹
^cFatigue includes asthenia and fatigue.¹
^dAbdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain, and hepatic pain.¹
^eVomiting includes retching and vomiting.¹
^fMusculoskeletal pain includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, non-cardiac chest pain, pain in extremity, and spinal pain.¹
^gDyspnea includes dyspnea, dyspnea at rest, and dyspnea exertional.¹
^hCough includes cough and productive cough.¹
ⁱRash includes rash, palmar-plantar erythrodysesthesia syndrome, rash maculo-papular, eczema, exfoliative rash, rash erythematous, rash pustular, skin exfoliation, dermatitis acneiform, drug eruption, dermatitis, rash pruritic, dermatitis bullous, toxic skin eruption.¹
^jPneumonia includes pneumonia, pneumonia aspiration, and pneumonia bacterial.¹

Laboratory abnormalities^1,a,k

Selected laboratory abnormalities (≥20%) from baseline in patients receiving TEPMETKO in descending order were: decreased albumin (81%), increased creatinine (60%), decreased lymphocytes (57%), increased ALP (52%), increased ALT (50%), increased AST (40%), decreased sodium (36%), decreased hemoglobin (31%), increased 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%)

Treatment modifications due to an AR in patients who received TEPMETKO¹

Dosage interruptions (53%): ARs which required dosage interruption in >2% of patients who received TEPMETKO included edema (28%), increased blood creatinine (6%), pleural effusion (3.5%), nausea (3.2%), increased ALT (2.9%), pneumonia (2.6%), decreased appetite (2.2%), and dyspnea (2.2%)
Dose reductions (36%): ARs which required dose reductions in >2% of patients who received TEPMETKO included edema (22%), increased blood creatinine (2.9%), fatigue (2.2%), and pleural effusion (2.2%)
Permanent discontinuation (25%): The most frequent adverse reactions (>1%) leading to permanent discontinuations of TEPMETKO were edema (8%), pleural effusion (1.6%), and general health deterioration (1.6%)

^aSeverity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.¹
^kThe denominator used to calculate the rate varied from 268 to 309 based on the number of patients with a baseline value and at least one posttreatment value.¹

Peripheral edema was observed with TEPMETKO and can be managed^1-3

Compensatory management of peripheral edema included²:

Limb elevation

Compression stockings

Dietary salt reduction

Diuretics

In VISION, edema was managed with²:

Dose reduction

Temporary interruption

Discontinuation

Refer to the full Prescribing Information for guidance on dose modifications.

TRAEs due to peripheral edema occurred in 67.1% of patients, with 11.2% experiencing Grade 3 or higher instances³
Proactive monitoring for peripheral edema is recommended²
TEPMETKO can be dose reduced in one step from two 225-mg tablets (450 mg total) to one 225-mg tablet¹

“

While edema may impact a patient's quality of life,
I find that it can be managed with supportive care.

”

— Robert Hsu, MD

A support kit is available to help your patients navigate their TEPMETKO treatment.

Request a Patient Support Kit

Review the dosing and administration for TEPMETKO

View dosing

ALP=alkaline phosphatase; ALT=alanine aminotransferase; AR=adverse reaction; AST=aspartate aminotransferase; GGT=gamma-glutamyl transferase; METex14+=mesenchymal-epithelial transition gene exon 14 skipping alterations; mNSCLC=metastatic non-small cell lung cancer; TRAEs=treatment-related adverse events.

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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