Description:
This study will look at how effective the study drug (tepotinib) is at stopping the growth
and spread of lung cancer. This study will also measure a number of other things including
safety of the study drug and the side effects, how body processes the study drug, or how the
study drug affects your quality of life. The study also has an optional pharmacogenetic
research part. Pharmacogenetic research is an important way to try to understand the role of
genetics in human disease and how genes impact the effectiveness of drugs, because
differences in genes can change the way a person responds to a particular drug.
Title
- Brief Title: Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)
- Official Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
MS200095-0022
- SECONDARY ID:
2015-005696-24
- NCT ID:
NCT02864992
Conditions
- Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer (NSCLC) With MET Exon 14 (METex14) Skipping Alterations or MET Amplification
Interventions
Drug | Synonyms | Arms |
---|
Tepotinib | | Tepotinib |
Purpose
This study will look at how effective the study drug (tepotinib) is at stopping the growth
and spread of lung cancer. This study will also measure a number of other things including
safety of the study drug and the side effects, how body processes the study drug, or how the
study drug affects your quality of life. The study also has an optional pharmacogenetic
research part. Pharmacogenetic research is an important way to try to understand the role of
genetics in human disease and how genes impact the effectiveness of drugs, because
differences in genes can change the way a person responds to a particular drug.
Detailed Description
The study includes 3 cohorts with one primary endpoint (Objective Response Rate). Enrollment
number and completion data is changed by new cohorts.
Trial Arms
Name | Type | Description | Interventions |
---|
Tepotinib | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
- Signed, written informed consent by subject or legal representative prior to any
trial-specific screening procedure
- Male or female, greater than or equal to (>=) 18 years of age (or having reached the
age of majority according to local laws and regulations
- Measurable disease confirmed by an independent review committee (IRC) in accordance
with RECIST version 1.1
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- A female subject is eligible to participate if she is not pregnant, not breastfeeding,
and at least one of the following conditions applies:
- Not a woman of childbearing potential OR
- A woman of childbearing potential who agrees to use a highly effective contraception
- A male subject must agree to use and to have their female partners of childbearing
potential to use a highly effective contraception
- Histologically or cytologically confirmed advanced (locally advanced or metastatic)
NSCLC (all types including squamous and sarcomatoid)
- Treatment naïve patients in first-line or pretreated patients with no more than 2
lines of prior therapy
- 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
Exclusion Criteria:
- Subjects with characterized Epidermal Growth Factor Receptor (EGFR) activating
mutations that predict sensitivity to anti-EGFR-therapy
- Subjects with characterized Anaplastic Lymphoma Kinase (ALK) rearrangements that
predict sensitivity to anti-ALK therapy
- Subjects with symptomatic brain metastases who are neurologically unstable
- Any unresolved toxicity Grade 2 or more according to National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE) from previous anticancer therapy
- Need for transfusion within 14 days prior to the first dose of trial treatment
- 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;
- Subjects who have brain metastasis as the only measurable lesion
- Inadequate hematological, liver, renal, cardiac function
- Prior treatment with other agents targeting the Hepatocyte Growth Factor c(HGF/c) -Met
pathway
- Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg)
- Past or current history of neoplasm other than Non-small Cell Lung Cancer (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 test product
- Major surgery within 28 days prior to Day 1 of trial treatment
- Known infection with human immunodeficiency virus, or an active infection with
hepatitis B or hepatitis C virus
- 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
- Known hypersensitivity to any of the trial treatment ingredients
- Legal incapacity or limited legal capacity
- Any other reason that, in the opinion of the Principal Investigator, precludes the
subject from participating in the trial
- Participation in another clinical trial within the past 30 days
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Objective response as assessed by independent review committee |
Time Frame: | Baseline up to 20 months |
Safety Issue: | |
Description: | Objective response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and as adjudicated by an Independent review committee. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
Secondary Outcome Measures
Measure: | Objective response assessed as per Investigator |
Time Frame: | Baseline up to 20 months |
Safety Issue: | |
Description: | Objective response will be determined according to RECIST 1.1 and as per investigator's discretion. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
Measure: | Duration of response as assessed by independent review committee |
Time Frame: | Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months |
Safety Issue: | |
Description: | Duration of response according to RECIST 1.1 and as adjudicated by an Independent review committee is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
Measure: | Duration of response as assessed by investigator |
Time Frame: | Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months |
Safety Issue: | |
Description: | Duration of response according to RECIST 1.1 and as per investigator's discretion is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
Measure: | Objective disease control as assessed by independent review committee |
Time Frame: | Baseline up to 20 months |
Safety Issue: | |
Description: | Objective disease control will be determined according to RECIST 1.1 and as adjudicated by an Independent review committee. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by independent review committee. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
Measure: | Objective disease control as assessed by investigator |
Time Frame: | Baseline up to 20 months |
Safety Issue: | |
Description: | Objective disease control will be determined according to RECIST 1.1 and as per investigator's discretion. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
Measure: | Progression free survival as assessed by independent review committee |
Time Frame: | Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months |
Safety Issue: | |
Description: | Progression free survival as assessed by independent review committee is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (based on independent review) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
Measure: | Progression free survival as assessed by investigator |
Time Frame: | Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months |
Safety Issue: | |
Description: | Progression free survival as assessed by investigator is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (as assessed by investigator) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. |
Measure: | Overall survival |
Time Frame: | Baseline until death, assessed up to 20 months |
Safety Issue: | |
Description: | Overall survival is defined as the time (in months) from first trial treatment administration to the date of death. |
Measure: | Occurrence of Treatment emergent adverse event (TEAEs) and deaths |
Time Frame: | From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 Months |
Safety Issue: | |
Description: | This outcome measure will be presented as the percentage of subjects with any (serious) adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator. |
Measure: | Percentage of subjects with of markedly abnormal clinical laboratory tests, vital signs, Electrocardiogram (ECG) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) |
Time Frame: | Baseline up to 20 months |
Safety Issue: | |
Description: | This outcome measure will be presented as the percentage of subjects with markedly abnormal vital sign measurements. Percentages are calculated using total number of subjects per treatment cohort as the denominator. Abnormalities in clinical laboratory tests will be measured as hematology and coagulation, biochemistry and urinalysis. Abnormalities in Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, body temperature as a part of vital signs; electrocardiogram (ECG) wave, body weight, and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), and clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis) will be assessed. |
Measure: | European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) |
Time Frame: | Baseline up to 20 months |
Safety Issue: | |
Description: | |
Measure: | European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) |
Time Frame: | Baseline up to 20 months |
Safety Issue: | |
Description: | |
Measure: | EuroQol Five Dimension Five Level Scale (EQ5D5L) |
Time Frame: | Baseline up to 20 months |
Safety Issue: | |
Description: | |
Measure: | Plasma concentrations of the drug |
Time Frame: | pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1 |
Safety Issue: | |
Description: | |
Measure: | Number of subjects with markedly abnormal clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis). |
Time Frame: | Baseline up to 20 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | EMD Serono Research & Development Institute, Inc. |
Trial Keywords
- lung
- neoplasm
- cancer
- tumor
- adenocarcinoma
- MET exon 14
- METex14
- pulmonary
- stage III
- stage IV
- c-Met
- cMET
- NSCLC
- advanced non-small cell lung cancer
- MET amplification
Last Updated
June 11, 2021