TEPMETKO
Generic: TEPOTINIB HYDROCHLORIDE
Basic Information
Manufacturer
EMD Serono, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
80a0f1b9-071a-47f5-9e67-32d638a669dc
Indications & Usage
1 INDICATIONS AND USAGE 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.
TEPMETKO is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition ( MET ) exon 14 skipping alterations.
( 1 )
TEPMETKO is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition ( MET ) exon 14 skipping alterations.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are described in greater detail elsewhere in the labeling: Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Pancreatic Toxicity [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥ 20%) were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.
The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased sodium, increased gamma-glutamyltransferase, increased amylase, increased lipase, increased ALT, increased AST, and decreased hemoglobin.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono at 1-800-283-8088 ext.
5563 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to TEPMETKO in 506 patients with solid tumors enrolled in five open-label, single-arm studies receiving TEPMETKO as single agent at a dose of 450 mg once daily.
This included 313 patients with NSCLC positive for MET ex14 skipping alterations, who received TEPMETKO in VISION.
Among 506 patients who received TEPMETKO, 44% were exposed for 6 months or longer, and 22% were exposed for more than one year.
The data described below reflect exposure to TEPMETKO 450 mg once daily in 313 patients with metastatic non-small cell lung cancer (NSCLC) with MET ex14 skipping alterations in VISION [see Clinical Studies (14) ].
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%).
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%).
Permanent discontinuation due to an adverse reaction occurred in 25% of patients who received TEPMETKO.
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%).
Dosage interruptions due to an adverse reaction occurred in 53% of patients who received TEPMETKO.
Adverse reactions 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 due to an adverse reaction occurred in 36% of patients who received TEPMETKO.
Adverse reactions 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%).
The most common adverse reactions (≥ 20%) in patients who received TEPMETKO were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.
The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased sodium, increased gamma-glutamyltransferase, increased amylase, increased lipase, increased ALT, increased AST, and decreased hemoglobin.
Table 2 summarizes the adverse reactions in VISION.
Table 2: Adverse Reactions in ≥ 10% of Patients with NSCLC with METex14 Skipping Alterations Who Received TEPMETKO in VISION Adverse Reactions TEPMETKO (N=313) All Grades Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
(%) Grades 3 to 4 (%) General disorders and administration-site conditions Edema Edema includes eye edema, face edema, generalized edema, localized edema, edema, genital edema, peripheral edema, peripheral swelling, periorbital edema, and scrotal edema.
81 16 Fatigue Fatigue includes asthenia and fatigue.
30 1.9 Gastrointestinal disorders Nausea 31 1.3 Diarrhea 29 0.6 Abdominal pain Abdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain, and hepatic pain.
19 0.6 Constipation 19 0.3 Vomiting Vomiting includes retching and vomiting.
15 1 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain Musculoskeletal pain includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, non-cardiac chest pain, pain in extremity, and spinal pain.
30 3.2 Respiratory, thoracic, and mediastinal disorders Dyspnea Dyspnea includes dyspnea, dyspnea at rest, and dyspnea exertional.
24 2.6 Cough Cough includes cough, and productive cough.
18 0.3 Pleural effusion 14 4.2 Metabolism and nutrition disorders Decreased appetite 21 1.9 Skin and Subcutaneous Tissue Disorders Rash Rash 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.
21 1.3 Infections and Infestations Pneumonia Pneumonia includes pneumonia, pneumonia aspiration, and pneumonia bacterial.
12 3.8 Clinically relevant adverse reactions in < 10% of patients who received TEPMETKO included ILD/pneumonitis, fever, dizziness, pruritus, and headache.
Table 3 summarizes the laboratory abnormalities observed in VISION.
Table 3: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients Who Received TEPMETKO in VISION Laboratory Abnormalities TEPMETKO The 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 post-treatment value.
Grades 1 to 4 Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
(%) Grades 3 to 4 (%) Chemistry Decreased albumin 81 9 Increased creatinine 60 1 Increased alkaline phosphatase aminotransferase 52 1.6 Increased alanine aminotransferase 50 4.9 Increased aspartate aminotransferase 40 3.6 Decreased sodium 36 9 Increased gamma-glutamyltransferase 29 6 Increased potassium 26 1.9 Increased amylase 25 5 Increased lipase 21 5 Hematology Decreased lymphocytes 57 15 Decreased hemoglobin 31 3.6 Decreased leukocytes 25 1.9 Decreased platelets 24 0.6 Increased Creatinine A median increase in serum creatinine of 30% was observed 21 days after initiation of treatment with TEPMETKO.
The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion .
The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased sodium, increased gamma-glutamyltransferase, increased amylase, increased lipase, increased ALT, increased AST, and decreased hemoglobin.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono at 1-800-283-8088 ext.
5563 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to TEPMETKO in 506 patients with solid tumors enrolled in five open-label, single-arm studies receiving TEPMETKO as single agent at a dose of 450 mg once daily.
This included 313 patients with NSCLC positive for MET ex14 skipping alterations, who received TEPMETKO in VISION.
Among 506 patients who received TEPMETKO, 44% were exposed for 6 months or longer, and 22% were exposed for more than one year.
The data described below reflect exposure to TEPMETKO 450 mg once daily in 313 patients with metastatic non-small cell lung cancer (NSCLC) with MET ex14 skipping alterations in VISION [see Clinical Studies (14) ].
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%).
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%).
Permanent discontinuation due to an adverse reaction occurred in 25% of patients who received TEPMETKO.
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%).
Dosage interruptions due to an adverse reaction occurred in 53% of patients who received TEPMETKO.
Adverse reactions 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 due to an adverse reaction occurred in 36% of patients who received TEPMETKO.
Adverse reactions 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%).
The most common adverse reactions (≥ 20%) in patients who received TEPMETKO were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.
The most common Grade 3 to 4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased albumin, decreased sodium, increased gamma-glutamyltransferase, increased amylase, increased lipase, increased ALT, increased AST, and decreased hemoglobin.
Table 2 summarizes the adverse reactions in VISION.
Table 2: Adverse Reactions in ≥ 10% of Patients with NSCLC with METex14 Skipping Alterations Who Received TEPMETKO in VISION Adverse Reactions TEPMETKO (N=313) All Grades Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
(%) Grades 3 to 4 (%) General disorders and administration-site conditions Edema Edema includes eye edema, face edema, generalized edema, localized edema, edema, genital edema, peripheral edema, peripheral swelling, periorbital edema, and scrotal edema.
81 16 Fatigue Fatigue includes asthenia and fatigue.
30 1.9 Gastrointestinal disorders Nausea 31 1.3 Diarrhea 29 0.6 Abdominal pain Abdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, gastrointestinal pain, and hepatic pain.
19 0.6 Constipation 19 0.3 Vomiting Vomiting includes retching and vomiting.
15 1 Musculoskeletal and Connective Tissue Disorders Musculoskeletal pain Musculoskeletal pain includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, non-cardiac chest pain, pain in extremity, and spinal pain.
30 3.2 Respiratory, thoracic, and mediastinal disorders Dyspnea Dyspnea includes dyspnea, dyspnea at rest, and dyspnea exertional.
24 2.6 Cough Cough includes cough, and productive cough.
18 0.3 Pleural effusion 14 4.2 Metabolism and nutrition disorders Decreased appetite 21 1.9 Skin and Subcutaneous Tissue Disorders Rash Rash 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.
21 1.3 Infections and Infestations Pneumonia Pneumonia includes pneumonia, pneumonia aspiration, and pneumonia bacterial.
12 3.8 Clinically relevant adverse reactions in < 10% of patients who received TEPMETKO included ILD/pneumonitis, fever, dizziness, pruritus, and headache.
Table 3 summarizes the laboratory abnormalities observed in VISION.
Table 3: Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients Who Received TEPMETKO in VISION Laboratory Abnormalities TEPMETKO The 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 post-treatment value.
Grades 1 to 4 Severity as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
(%) Grades 3 to 4 (%) Chemistry Decreased albumin 81 9 Increased creatinine 60 1 Increased alkaline phosphatase aminotransferase 52 1.6 Increased alanine aminotransferase 50 4.9 Increased aspartate aminotransferase 40 3.6 Decreased sodium 36 9 Increased gamma-glutamyltransferase 29 6 Increased potassium 26 1.9 Increased amylase 25 5 Increased lipase 21 5 Hematology Decreased lymphocytes 57 15 Decreased hemoglobin 31 3.6 Decreased leukocytes 25 1.9 Decreased platelets 24 0.6 Increased Creatinine A median increase in serum creatinine of 30% was observed 21 days after initiation of treatment with TEPMETKO.
The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion .