Clinical Trials /

Tepotinib Phase II in Non-small Cell Lung Cancer (NSCLC) Harboring MET Alterations

NCT02864992

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

    <li>Brief Title: Tepotinib Phase II in Non-small Cell Lung Cancer (NSCLC) Harboring MET Alterationsli><li>Official Title: A Phase II, Single-arm Trial to Investigate Tepotinib in Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer With MET Exon 14 (METex14) Skipping Alterations or MET Amplification (VISION)li>

Clinical Trial IDs

    <li>ORG STUDY ID: MS200095-0022li><li>SECONDARY ID: 2015-005696-24li><li>NCT ID: NCT02864992li>

Conditions

    <li>Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer With MET Exon 14 (METex14) Skipping Alterations or MET Amplificationli>

Interventions

DrugSynonymsArms
TepotinibTepotinib

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.

Trial Arms

NameTypeDescriptionInterventions
TepotinibExperimental
    <li>Tepotinibli>

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 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 confirmed advanced (Stage IIIB/IV) Non-small Cell Lung Cancer (NSCLC)
             (all histologies 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, or MET amplification only in plasma and/or tumor biopsy samplet

        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

          -  Active brain metastases

          -  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:Maximum Plasma concentration (Cmax) of 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:Trough plasma concentration (Ctrough) of 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:Recruiting
Lead Sponsor:EMD Serono Research &amp; Development Institute, Inc.

Trial Keywords

    <li>lungli><li>neoplasmli><li>cancerli><li>tumorli><li>adenocarcinomali><li>MET exon 14li><li>METex14li><li>pulmonaryli><li>stage IIIli><li>stage IVli><li>c-Metli><li>cMETli><li>NSCLCli><li>advanced non-small cell lung cancerli><li>MET amplificationli>

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