Clinical Trials List
Protocol NumberMS200095-0022
NCT Number(ClinicalTrials.gov Identfier)NCT02864992
2018-07-18 - 2021-08-31
Phase II
Recruiting2
Terminated4
ICD-10C34
Malignant neoplasm of bronchus and lung
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Phase II Single-arm Trial to Investigate Tepotinib in Advanced (Locally Advanced or Metastatic) Non-small Cell Lung Cancer With METex14 Skipping Alterations or MET Amplification (VISION)
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Merck KGaA
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chih-Yen Tu Division of Thoracic Medicine
- Wen-Chien Cheng Division of Thoracic Medicine
- 廖偉志 Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jen-Fu Shih Division of Thoracic Medicine
- Chi-Lu Chiang Division of Thoracic Medicine
- Chao-Hua Chiu Division of Thoracic Medicine
- Heng-Sheng Chao Division of Thoracic Medicine
- 趙恒勝 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
4 Recruiting
Audit
None
Co-Principal Investigator
- 林孟志 Division of Thoracic Medicine
- 賴建豪 Division of Thoracic Medicine
- 李易濰 Division of Thoracic Medicine
- Chia-Cheng Tseng Division of Thoracic Medicine
- 黃國棟 Division of Thoracic Medicine
- Shau-Hsuan Li Division of Thoracic Medicine
- 王逸熙 Division of Thoracic Medicine
- 鍾聿修 Division of Thoracic Medicine
- 林理涵 Division of Thoracic Medicine
- 張晃智 Division of Thoracic Medicine
- 趙東瀛 Division of Thoracic Medicine
- 陳彥豪 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 林宗哲 Division of Hematology & Oncology
- JIN-YUAN SHIH Division of Hematology & Oncology
- 許嘉林 Division of Hematology & Oncology
- 吳尚俊 Division of Hematology & Oncology
- Jih-Hsiang Lee Division of Hematology & Oncology
- Chong-Jen Yu Division of Hematology & Oncology
- 廖唯昱 Division of Hematology & Oncology
- YEN-TING LIN Division of Hematology & Oncology
- Chia-Chi Lin Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- 陳冠宇 Division of Hematology & Oncology
- 蔡子修 Division of Hematology & Oncology
- 林育麟 Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Hematology & Oncology
- 楊景堯 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 張山岳 Division of Thoracic Medicine
- 唐士恩 Division of Thoracic Medicine
- 吳世偉 Division of Thoracic Medicine
- 彭忠衎 Division of Thoracic Medicine
- 陳盈潔 Division of Thoracic Medicine
- 孟繁俊 Division of Thoracic Medicine
- 簡志峰 Division of Thoracic Medicine
- 沈志浩 Division of Thoracic Medicine
- 蔡文銓 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- KUO-HSUAN HSU Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
- YEN-HSIANG HUANG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Non-small Cell Lung Cancer
Objectives
Primary Objectives
Cohort A (METex14 skipping alterations):
To assess the efficacy of tepotinib in subjects with advanced (Stage III/IV) NSCLC, as per
objective response (confirmed complete response [CR] or partial response [PR]) determined
according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, based on
independent review in:
Subjects tested positive for METex14 skipping alterations, regardless of MET amplification
status
Subjects tested positive for METex14 skipping alterations based on the LBx analysis set,
regardless of MET amplification status
Subjects tested positive for METex14 skipping alterations based on the TBx analysis set,
regardless of MET amplification status.
Cohort B (MET amplification):
To assess the efficacy of tepotinib in subjects with advanced (Stage III/IV) NSCLC, as per
objective response (confirmed complete response [CR] or partial response [PR]) determined
according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, based on
independent review in:
Subjects tested positive for MET amplification in LBx and negative for METex14 skipping
alterations.
Test Drug
tepotinib
Active Ingredient
tepotinib
Dosage Form
film coated tablets
film coated tablets
film coated tablets
film coated tablets
film coated tablets
Dosage
100
500
250
500
250
Endpoints
Primary Endpoint
The primary endpoint is objective response (confirmed CR or PR) determined according to
RECIST Version 1.1, based on independent review (IRC).
Subjects are identified as having an objective response if they achieve either a confirmed CR or
PR from first administration of trial treatment to first observation of PD. Confirmation needs to
take place by a tumor assessment at least 4 weeks (28 days) after the tumor assessments initially
indicating CR or PR.
The primary endpoint is objective response (confirmed CR or PR) determined according to
RECIST Version 1.1, based on independent review (IRC).
Subjects are identified as having an objective response if they achieve either a confirmed CR or
PR from first administration of trial treatment to first observation of PD. Confirmation needs to
take place by a tumor assessment at least 4 weeks (28 days) after the tumor assessments initially
indicating CR or PR.
Inclution Criteria
Inclusion Criteria
3. Signed, written informed consent by subject or legal representative prior to any trial-specific
screening procedure;
4. Male or female, ≥ 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]);
5. Measurable disease in accordance with RECIST Version 1.1;
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1;
7. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least
1 of the following conditions applies:
a. Not a woman of childbearing potential as defined in Appendix VIII
OR
b. A woman of childbearing potential who agrees to use a highly effective contraception
(ie, methods with a failure rate of less than 1% per year) as detailed in in Appendix VIII of this
protocol 2 weeks before start of first dose of study treatment, during the treatment period and
for at least 4 weeks after the last dose of study treatment. Women of childbearing potential
must have a negative pregnancy test (β-HCG test in serum) prior to enrolment.
8. A male subject must agree to use and to have their female partners of childbearing potential to
use a highly effective contraception (ie, methods with a failure rate of less than 1% per year)
as detailed in Appendix VIII of this protocol from the first dose of study treatment, during the
treatment period and for at least 3 months after the last dose of study treatment and refrain
from donating sperm during this period. Male subjects should always use a barrier method
such as condom concomitantly.
9. Histologically confirmed advanced (Stage IIIB/IV) NSCLC (all histologies including
squamous and sarcomatoid);
10. Treatment naïve patients in first-line or pretreated patients with no more than 2 lines of prior
therapy;
11. Subjects with MET alterations, namely
METex14 skipping alterations in plasma and/or tissue, as determined by the central
laboratory or by an assay with appropriate regulatory status will, be enrolled into the trial.
For these subjects, sufficient tumor tissue and/or plasma is requested to allow additional
testing
MET amplification only in plasma defined by a positive LBx test, as determined by the
central laboratory or by an assay with appropriate regulatory status
Based on the outcome of the interim analysis in 12 LBx selected subjects: MET
amplification only in tissue defined by a positive TBx with a gain of at least 4 copies of the
MET gene, as determined by the central laboratory or by an assay with appropriate
regulatory status.
3. Signed, written informed consent by subject or legal representative prior to any trial-specific
screening procedure;
4. Male or female, ≥ 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]);
5. Measurable disease in accordance with RECIST Version 1.1;
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1;
7. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least
1 of the following conditions applies:
a. Not a woman of childbearing potential as defined in Appendix VIII
OR
b. A woman of childbearing potential who agrees to use a highly effective contraception
(ie, methods with a failure rate of less than 1% per year) as detailed in in Appendix VIII of this
protocol 2 weeks before start of first dose of study treatment, during the treatment period and
for at least 4 weeks after the last dose of study treatment. Women of childbearing potential
must have a negative pregnancy test (β-HCG test in serum) prior to enrolment.
8. A male subject must agree to use and to have their female partners of childbearing potential to
use a highly effective contraception (ie, methods with a failure rate of less than 1% per year)
as detailed in Appendix VIII of this protocol from the first dose of study treatment, during the
treatment period and for at least 3 months after the last dose of study treatment and refrain
from donating sperm during this period. Male subjects should always use a barrier method
such as condom concomitantly.
9. Histologically confirmed advanced (Stage IIIB/IV) NSCLC (all histologies including
squamous and sarcomatoid);
10. Treatment naïve patients in first-line or pretreated patients with no more than 2 lines of prior
therapy;
11. Subjects with MET alterations, namely
METex14 skipping alterations in plasma and/or tissue, as determined by the central
laboratory or by an assay with appropriate regulatory status will, be enrolled into the trial.
For these subjects, sufficient tumor tissue and/or plasma is requested to allow additional
testing
MET amplification only in plasma defined by a positive LBx test, as determined by the
central laboratory or by an assay with appropriate regulatory status
Based on the outcome of the interim analysis in 12 LBx selected subjects: MET
amplification only in tissue defined by a positive TBx with a gain of at least 4 copies of the
MET gene, as determined by the central laboratory or by an assay with appropriate
regulatory status.
Exclusion Criteria
Exclusion Criteria
Cancer-related
3. Active brain metastases (defined as neurologically stable for < 4 weeks and/or symptomatic
and/or requiring treatment with steroids and/or leptomeningeal disease). Subjects must have
completed any prior treatment for brain metastases ≥ 4 weeks prior to start of therapy
(≥ 2 weeks for stereotactic radiosurgery/gamma knife). Subjects who are neurologically stable
on symptomatic therapy with anticonvulsants with low drug interaction risk or whose steroids
are being tapered are eligible. Asymptomatic untreated brain metastases ≤ 1cm of longest
diameter are eligible;
4. Any unresolved toxicity Grade 2 or more according to National Cancer Institute-Common
Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03, from previous
anticancer therapy;
5. Need for transfusion within 14 days prior to the first dose of trial treatment;
7. Subjects who have brain metastasis as the only measurable lesion.
23. Subjects with characterized EGFR activating mutations that predict sensitivity to anti-EGFR
therapy;
24. Subjects with characterized ALK rearrangements that predict sensitivity to anti-ALK therapy;
25. Prior chemotherapy, biological therapy, radiation therapy, hormonal therapy for anti-cancer
purposes, targeted therapy, or other investigational anticancer therapy (not including palliative
radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment.
Laboratory values and organ function
8. Inadequate hematological function:
Hemoglobin < 8.5 g/dL
Neutrophils < 1.5 × 109/L
Platelets < 100 × 109/L.
9. Inadequate liver function: total bilirubin > 1.5 × upper limit of normal (ULN); Aspartate
aminotransferase (AST)/alanine aminotransferase (ALT) > 3 × ULN; For subjects with liver
metastases: total bilirubin > 1.5 × ULN, AST/ALT > 5 × ULN
10. Inadequate renal function:
Severe renal impairment as evidenced by:
Serum creatinine 1.5 × ULN
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 <
30 mL/min. In such case, subjects with 24 hour CrCl < 30 mL/min should be excluded)
General
11. Prior treatment with other agents targeting the HGF/c-Met pathway;
12. Impaired cardiac function
a. Left ventricular ejection fraction < 45% defined by echocardiography (a screening
assessment not required for subjects without a history of congestive heart failure
unless clinically indicated)
b. Serious arrhythmia
c. Unstable angina pectoris
d. New York Heart Association heart failure class III and IV
e. Myocardial infarction within the last 12 months prior to trial entry
f. Symptomatic pericardial effusion
13. Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg)
14. 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
15. Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal
disease, or conditions that may hamper compliance and/or absorption of the test product
16. Major surgery within 28 days prior to Day 1 of trial treatment
17. Known infection with human immunodeficiency virus, or an active infection with hepatitis B
or hepatitis C virus
18. Substance abuse, active infection, or other acute or chronic medical or psychiatric condition or
laboratory abnormalities that might increase the risk associated with trial participation at the
discretion of Investigators
19. Known hypersensitivity to any of the trial treatment ingredients
20. Legal incapacity or limited legal capacity
21. Any other reason that, in the opinion of the Principal Investigator, precludes the subject from
participating in the trial
22. Participation in another clinical trial within the past 30 days.
Cancer-related
3. Active brain metastases (defined as neurologically stable for < 4 weeks and/or symptomatic
and/or requiring treatment with steroids and/or leptomeningeal disease). Subjects must have
completed any prior treatment for brain metastases ≥ 4 weeks prior to start of therapy
(≥ 2 weeks for stereotactic radiosurgery/gamma knife). Subjects who are neurologically stable
on symptomatic therapy with anticonvulsants with low drug interaction risk or whose steroids
are being tapered are eligible. Asymptomatic untreated brain metastases ≤ 1cm of longest
diameter are eligible;
4. Any unresolved toxicity Grade 2 or more according to National Cancer Institute-Common
Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03, from previous
anticancer therapy;
5. Need for transfusion within 14 days prior to the first dose of trial treatment;
7. Subjects who have brain metastasis as the only measurable lesion.
23. Subjects with characterized EGFR activating mutations that predict sensitivity to anti-EGFR
therapy;
24. Subjects with characterized ALK rearrangements that predict sensitivity to anti-ALK therapy;
25. Prior chemotherapy, biological therapy, radiation therapy, hormonal therapy for anti-cancer
purposes, targeted therapy, or other investigational anticancer therapy (not including palliative
radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment.
Laboratory values and organ function
8. Inadequate hematological function:
Hemoglobin < 8.5 g/dL
Neutrophils < 1.5 × 109/L
Platelets < 100 × 109/L.
9. Inadequate liver function: total bilirubin > 1.5 × upper limit of normal (ULN); Aspartate
aminotransferase (AST)/alanine aminotransferase (ALT) > 3 × ULN; For subjects with liver
metastases: total bilirubin > 1.5 × ULN, AST/ALT > 5 × ULN
10. Inadequate renal function:
Severe renal impairment as evidenced by:
Serum creatinine 1.5 × ULN
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 <
30 mL/min. In such case, subjects with 24 hour CrCl < 30 mL/min should be excluded)
General
11. Prior treatment with other agents targeting the HGF/c-Met pathway;
12. Impaired cardiac function
a. Left ventricular ejection fraction < 45% defined by echocardiography (a screening
assessment not required for subjects without a history of congestive heart failure
unless clinically indicated)
b. Serious arrhythmia
c. Unstable angina pectoris
d. New York Heart Association heart failure class III and IV
e. Myocardial infarction within the last 12 months prior to trial entry
f. Symptomatic pericardial effusion
13. Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg)
14. 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
15. Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal
disease, or conditions that may hamper compliance and/or absorption of the test product
16. Major surgery within 28 days prior to Day 1 of trial treatment
17. Known infection with human immunodeficiency virus, or an active infection with hepatitis B
or hepatitis C virus
18. Substance abuse, active infection, or other acute or chronic medical or psychiatric condition or
laboratory abnormalities that might increase the risk associated with trial participation at the
discretion of Investigators
19. Known hypersensitivity to any of the trial treatment ingredients
20. Legal incapacity or limited legal capacity
21. Any other reason that, in the opinion of the Principal Investigator, precludes the subject from
participating in the trial
22. Participation in another clinical trial within the past 30 days.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
106 participants
