Clinical Trials List
Protocol NumberMS200095-0031
NCT Number(ClinicalTrials.gov Identfier)NCT03940703
Completed
2019-12-01 - 2024-12-31
Phase II
Recruiting7
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase II, two arm study to investigate tepotinib combined with osimertinib in MET amplified, advanced or metastatic non-small cell lung cancer (NSCLC) harboring activating EGFR mutations and having acquired resistance to prior osimertinib therapy (INSIGHT 2 Study)
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Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Merck Healthcare KGaA
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Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 陳焜結 Division of Thoracic Medicine
- Gee-chen Chang Division of Thoracic Medicine
- YEN-HSIANG HUANG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Heng-Sheng Chao Division of Thoracic Medicine
- Chi-Lu Chiang Division of Thoracic Medicine
- 趙恒勝 Division of Thoracic Medicine
- 楊朝能 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林孟志 Division of Thoracic Medicine
- 賴建豪 Division of Thoracic Medicine
- 李易濰 Division of Radiology
- 陳怡豪 Division of Ophthalmology
- Chia-Cheng Tseng Division of Thoracic Medicine
- 黃國棟 Division of Thoracic Medicine
- Shau-Hsuan Li Division of Hematology & Oncology
- 王逸熙 Division of Thoracic Medicine
- 鍾聿修 Division of Thoracic Medicine
- 林理涵 Division of Radiology
- 張晃智 Division of Thoracic Medicine
- 趙東瀛 Division of Thoracic Medicine
- 陳彥豪 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林建良 Division of Hematology & Oncology
- 蕭聖諺 Division of Hematology & Oncology
- 黃文聰 Division of Hematology & Oncology
- 陳彥勳 Division of Hematology & Oncology
- Shang-Wen Chen Division of Hematology & Oncology
- 高婉真 Division of Hematology & Oncology
- 曹朝榮 Division of Hematology & Oncology
- 林正耀 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
- 廖唯昱 Division of General Internal Medicine
- 吳尚俊 Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- 徐偉勛 醫學研究部
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- 楊景堯 Division of General Internal Medicine
- 林育麟 Division of Hematology & Oncology
- 林宗哲 Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
- 魏以宣 Division of Ophthalmology
- 廖斌志 Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- YEN-TING LIN Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 廖偉志 Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
- Wen-Chien Cheng Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
non-small cell lung cancer(NSCLC)
Objectives
Primary Objectives
To confirm a safe and tolerable
Phase II dose (RP2D) of tepotinib
when used in combination with
osimertinib.
To assess the efficacy of tepotinib
combined with osimertinib in
participants with advanced or
metastatic NSCLC.
Secondary Objectives
To assess tolerability and safety.
To further assess efficacy.
To assess health related quality of life.
Pharmacokinetics
To assess resistance marker
related to EGFR and other
molecular pathways in circulating
tumor deoxyribonucleic acid
(ctDNA) at baseline and
progression.
Test Drug
Tepotinib
Active Ingredient
Tepotinib
Dosage Form
Film-coated Tablet
Dosage
250
Endpoints
Occurrence of dose limiting toxicities (DLTs) during the first treatment cycle.
Objective response (confirmed complete response
[CR] or partial response [PR]) determined according
to Response Evaluation Criteria in Solid Tumors
(RECIST) Version 1.1 as per Independent Review
Committee (IRC).
Occurrence of TEAEs and treatment-related AEs
according to National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events
(CTCAE) v5.0, and deaths.
Occurrence of abnormalities (Grade ≥ 3) in
laboratory test values (hematology and coagulation,
biochemistry) and urinalysis.
Occurrence of markedly abnormal vital sign
measurements, change in body weight, and Eastern
Cooperative Oncology Group (ECOG) performance
status.
Occurrence of clinically significantly abnormal
electrocardiograms (ECGs).
Objective response according to RECIST 1.1
assessed by Investigator.
Confirmed CR assessed by IRC and by Investigator.
Duration of response assessed from CR or PR until
PD, death, or last tumor assessment assessed by IRC
and by Investigator.
Disease control (confirmed CR + PR or stable
disease [SD] lasting at least 12 weeks) as assessed by
IRC and by Investigator.
Progression free survival time according to
RECIST 1.1 by IRC and by Investigator.
Overall survival.
Patient-reported outcomes/health-related quality of
life as reported using the following:
EuroQol Five Dimension Five Level Scale
European Organisation for Research and
Treatment of Cancer Quality of Life
Questionnaire C30
Non–small Cell Lung Cancer Symptom
Assessment Questionnaire.
Single- and multiple-dose PK profile of osimertinib,
tepotinib, and their metabolites including but not
limited to AUC0-t, Cmax, and tmax after first dose (Day
1) and after multiple study intervention dose
administrations (Day 15) (safety run-in).
Population PK profile of osimertinib, tepotinib, and
their metabolites, including, but not limited to, CL/f
and VZ/f based on sparse PK sampling on Day 1,
Cycle 1 and 2.
Mutation status in EGFR and other pathways.
Objective response (confirmed complete response
[CR] or partial response [PR]) determined according
to Response Evaluation Criteria in Solid Tumors
(RECIST) Version 1.1 as per Independent Review
Committee (IRC).
Occurrence of TEAEs and treatment-related AEs
according to National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events
(CTCAE) v5.0, and deaths.
Occurrence of abnormalities (Grade ≥ 3) in
laboratory test values (hematology and coagulation,
biochemistry) and urinalysis.
Occurrence of markedly abnormal vital sign
measurements, change in body weight, and Eastern
Cooperative Oncology Group (ECOG) performance
status.
Occurrence of clinically significantly abnormal
electrocardiograms (ECGs).
Objective response according to RECIST 1.1
assessed by Investigator.
Confirmed CR assessed by IRC and by Investigator.
Duration of response assessed from CR or PR until
PD, death, or last tumor assessment assessed by IRC
and by Investigator.
Disease control (confirmed CR + PR or stable
disease [SD] lasting at least 12 weeks) as assessed by
IRC and by Investigator.
Progression free survival time according to
RECIST 1.1 by IRC and by Investigator.
Overall survival.
Patient-reported outcomes/health-related quality of
life as reported using the following:
EuroQol Five Dimension Five Level Scale
European Organisation for Research and
Treatment of Cancer Quality of Life
Questionnaire C30
Non–small Cell Lung Cancer Symptom
Assessment Questionnaire.
Single- and multiple-dose PK profile of osimertinib,
tepotinib, and their metabolites including but not
limited to AUC0-t, Cmax, and tmax after first dose (Day
1) and after multiple study intervention dose
administrations (Day 15) (safety run-in).
Population PK profile of osimertinib, tepotinib, and
their metabolites, including, but not limited to, CL/f
and VZ/f based on sparse PK sampling on Day 1,
Cycle 1 and 2.
Mutation status in EGFR and other pathways.
Inclution Criteria
Inclusion Criteria:
Age
1. Are ≥ 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18 years of age [ie, ≥ 20 years of age in Japan]), at the time of signing the informed consent.
2. Are participants with the following:
a) Locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) histology (confirmed by either histology or cytology) with documented activating Epidermal Growth Factor Receptor (EGFR) mutation
b) Presence of at least 1 independently verified measurable lesion in accordance with RECIST 1.1, that can be accurately assessed at baseline with ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), which is suitable for accurate repeated measurements and that preferably was not previously irradiated or biopsied
c) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum life expectancy of 12 weeks
d) Acquired resistance on previous first-line osimertinib. Participants must meet both of the following 2 criteria:
Radiological documentation of disease progression on first-line osimertinib
Objective clinical benefit documented during previous osimertinib therapy, defined by either partial or complete radiological response, or durable stable disease (SD) (SD should last greater than (>) 6 months after initiation of osimertinib
e) Have received only first-line osimertinib as a prior line of therapy in the non curative advanced or metastatic NSCLC setting
f) MET amplification as determined by either FISH testing (central or local) on tumor tissue (TBx) or central blood-based next generation sequencing (LBx). Tumor and blood samples must be collected following progression on prior first-line osimertinib at Prescreening
Submission of tumor tissue and blood sample obtained after progression on first-line osimertinib, is mandatory for all patients for MET amplification testing
Submission of tumor tissue during Prescreening or Screening is mandatory for patients with tumor tissue tested by local FISH, to confirm MET amplification status. Central confirmation is not mandated prior to the start of study treatment
Other protocol defined inclusion criteria could apply
Age
1. Are ≥ 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18 years of age [ie, ≥ 20 years of age in Japan]), at the time of signing the informed consent.
2. Are participants with the following:
a) Locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) histology (confirmed by either histology or cytology) with documented activating Epidermal Growth Factor Receptor (EGFR) mutation
b) Presence of at least 1 independently verified measurable lesion in accordance with RECIST 1.1, that can be accurately assessed at baseline with ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), which is suitable for accurate repeated measurements and that preferably was not previously irradiated or biopsied
c) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum life expectancy of 12 weeks
d) Acquired resistance on previous first-line osimertinib. Participants must meet both of the following 2 criteria:
Radiological documentation of disease progression on first-line osimertinib
Objective clinical benefit documented during previous osimertinib therapy, defined by either partial or complete radiological response, or durable stable disease (SD) (SD should last greater than (>) 6 months after initiation of osimertinib
e) Have received only first-line osimertinib as a prior line of therapy in the non curative advanced or metastatic NSCLC setting
f) MET amplification as determined by either FISH testing (central or local) on tumor tissue (TBx) or central blood-based next generation sequencing (LBx). Tumor and blood samples must be collected following progression on prior first-line osimertinib at Prescreening
Submission of tumor tissue and blood sample obtained after progression on first-line osimertinib, is mandatory for all patients for MET amplification testing
Submission of tumor tissue during Prescreening or Screening is mandatory for patients with tumor tissue tested by local FISH, to confirm MET amplification status. Central confirmation is not mandated prior to the start of study treatment
Other protocol defined inclusion criteria could apply
Exclusion Criteria
Exclusion Criteria:
Spinal cord compression or brain metastasis unless asymptomatic, stable or not requiring steroids for at least 2 weeks prior to start of study intervention
Any unresolved toxicity Grade 2 or more according to National cancer institute common terminology criteria for adverse events( NCI-CTCAE) version 5, from previous anticancer therapy with the exception of alopecia
Need for transfusion within 14 days prior to the first dose of study intervention
Participants who have brain metastasis as the only measurable lesion
Inadequate hematological function: Hemoglobin < 8.5 g/dL ; Neutrophils < 1.5 × 109/L ; Platelets < 100 × 109/L
Inadequate liver function: Total bilirubin > 1.5 × ULN ; AST/ALT/ALP > 3 × ULN ; For participants with liver metastases:
Total bilirubin > 1.5 × ULN ; AST/ALT/ALP > 5 × ULN ; For participants with bone metastases: ALP > 5 × ULN
Inadequate renal function: Renal impairment as evidenced by serum creatinine 1.5 × ULN, or creatinine clearance (CrCl) < 30 mL/min calculated by the Cockcroft-Gault formula (24-hour CrCl might be requested by the Investigator for confirmation, if calculated CrCl is < 50 mL/min. In such case, participants with 24-hour CrCl < 30 mL/min should be excluded).
CrCl (mL/min) = [(140 – age(year)) × weight(kg)] / 72 × serum creatinine (mg/dL) {× 0.85 for females}
History of ILD or interstitial pneumonitis including radiation pneumonitis that required steroid treatment.
Impaired cardiac function: Left ventricular ejection fraction < 45% defined by echocardiography; Serious arrhythmia; Unstable angina pectoris; Congestive Heart Failure New York Heart Association III and IV ; Myocardial infarction, stroke, or transient ischemic attack within the last
6 months prior to study entry.
Corrected QT interval (QTcF) > 470 ms for women and > 450 ms for men at screening. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such
as hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes.
Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg).
Contraindication to the administration of osimertinib.
Medical history of liver fibrosis/cirrhosis.
Past or current history of neoplasm other than NSCLC, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years.
Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product.
Major surgery within 28 days prior to Day 1 of study intervention.
Known human immunodeficiency virus positivity.
Known hypersensitivity to any of the study intervention ingredients.
Prior/Concomitant Therapy
Prior treatment with other agents targeting the HGF/MET pathway such as crizotinib,capmatinib, savolitinib, foretinib, glesatinib, cabozantinib, merestinib, onartuzumab, rilotumumab, emibetuzumab, and ficlatuzumab.
Participants currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of study intervention) medications or herbal supplements known to be potent inducers of CYP3A4.
Prior/Concurrent Clinical Study Experience
Participation in another interventional clinical study (except those participants who were solely involved in other studies where the investigational product was a 1st, 2nd, or 3rd generation EGFR-TKI) within the 30 days prior to randomization/first dose.
Other Exclusions
Substance abuse, active infection, or other acute or chronic medical or psychiatric condition or laboratory abnormalities that might increase the risk associated with study participation at the discretion of Investigators.
Legal incapacity or limited legal capacity.
Any other reason that, in the opinion of the Principal Investigator, precludes the participant from participating in the study.
Inadequate hematological, liver and renal function
Impaired cardiac function
History of interstitial lung disease(ILD) or interstitial pneumonitis including radiation pneumonitis that required steroid treatment
Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 millimeter of mercury (mmHg)
Contraindication to the administration of osimertinib
Other protocol defined exclusion criteria could apply.
Spinal cord compression or brain metastasis unless asymptomatic, stable or not requiring steroids for at least 2 weeks prior to start of study intervention
Any unresolved toxicity Grade 2 or more according to National cancer institute common terminology criteria for adverse events( NCI-CTCAE) version 5, from previous anticancer therapy with the exception of alopecia
Need for transfusion within 14 days prior to the first dose of study intervention
Participants who have brain metastasis as the only measurable lesion
Inadequate hematological function: Hemoglobin < 8.5 g/dL ; Neutrophils < 1.5 × 109/L ; Platelets < 100 × 109/L
Inadequate liver function: Total bilirubin > 1.5 × ULN ; AST/ALT/ALP > 3 × ULN ; For participants with liver metastases:
Total bilirubin > 1.5 × ULN ; AST/ALT/ALP > 5 × ULN ; For participants with bone metastases: ALP > 5 × ULN
Inadequate renal function: Renal impairment as evidenced by serum creatinine 1.5 × ULN, or creatinine clearance (CrCl) < 30 mL/min calculated by the Cockcroft-Gault formula (24-hour CrCl might be requested by the Investigator for confirmation, if calculated CrCl is < 50 mL/min. In such case, participants with 24-hour CrCl < 30 mL/min should be excluded).
CrCl (mL/min) = [(140 – age(year)) × weight(kg)] / 72 × serum creatinine (mg/dL) {× 0.85 for females}
History of ILD or interstitial pneumonitis including radiation pneumonitis that required steroid treatment.
Impaired cardiac function: Left ventricular ejection fraction < 45% defined by echocardiography; Serious arrhythmia; Unstable angina pectoris; Congestive Heart Failure New York Heart Association III and IV ; Myocardial infarction, stroke, or transient ischemic attack within the last
6 months prior to study entry.
Corrected QT interval (QTcF) > 470 ms for women and > 450 ms for men at screening. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such
as hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes.
Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg).
Contraindication to the administration of osimertinib.
Medical history of liver fibrosis/cirrhosis.
Past or current history of neoplasm other than NSCLC, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years.
Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product.
Major surgery within 28 days prior to Day 1 of study intervention.
Known human immunodeficiency virus positivity.
Known hypersensitivity to any of the study intervention ingredients.
Prior/Concomitant Therapy
Prior treatment with other agents targeting the HGF/MET pathway such as crizotinib,capmatinib, savolitinib, foretinib, glesatinib, cabozantinib, merestinib, onartuzumab, rilotumumab, emibetuzumab, and ficlatuzumab.
Participants currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of study intervention) medications or herbal supplements known to be potent inducers of CYP3A4.
Prior/Concurrent Clinical Study Experience
Participation in another interventional clinical study (except those participants who were solely involved in other studies where the investigational product was a 1st, 2nd, or 3rd generation EGFR-TKI) within the 30 days prior to randomization/first dose.
Other Exclusions
Substance abuse, active infection, or other acute or chronic medical or psychiatric condition or laboratory abnormalities that might increase the risk associated with study participation at the discretion of Investigators.
Legal incapacity or limited legal capacity.
Any other reason that, in the opinion of the Principal Investigator, precludes the participant from participating in the study.
Inadequate hematological, liver and renal function
Impaired cardiac function
History of interstitial lung disease(ILD) or interstitial pneumonitis including radiation pneumonitis that required steroid treatment
Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 millimeter of mercury (mmHg)
Contraindication to the administration of osimertinib
Other protocol defined exclusion criteria could apply.
The Estimated Number of Participants
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Taiwan
12 participants
-
Global
120 participants
