Stage IIIB/IV adenocarcinoma of the lung with MET exon 14 (METex14) skipping alterations
Conditions
Interventions
Product Name: tepotinib
Product Code: MSC2156119J
Pharmaceutical Form: Tablet
INN or Proposed INN: tepotinib
Current Sponsor code: MSC2156119J
Other descriptive name: MSC2156119J
Concentration unit: m
Sponsors
Merck KGaA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: "1. Histologically confirmed advanced adenocarcinoma of the lung, having failed at least one line of systemic therapy, including a platinum-doublet-containing regimen, but having failed a maximum of 2 lines of active therapy; 2. METex14 skipping alterations, as determined by the central laboratory. Both, archival and fresh biopsies are acceptable; In case METex14 skipping alteration has been observed in a subject in a pre-trial setting, it should be ensured that sufficient tissue is available for re-testing before trial entry. Only subjects with METex14 skipping mutation based on trial central testing will be enrolled into the trial. 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); 5. Measurable disease in accordance with RECIST version 1.1; 6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1." Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Subjects with characterized EGFR (documented results; local testing acceptable) that predict sensitivity to EGFR-therapy, including, but not limited to exon 19 deletions and exon 21 alterations; 2. Subjects with characterized ALK rearrangements (documented results; local testing acceptable); 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 are eligible; 4. Any unresolved toxicity Grade 2 or more according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) from previous anticancer therapy; 5. Need for transfusion within 14 days prior to the first dose of trial treatment; 6. Prior chemotherapy, biological therapy, radiation therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment; 7. Inadequate hematological, liver, renal, cardiac function; 8. Prior treatment with other agents targeting the HGF/c-Met pathway; 9. 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 (for a full list of exlustion criteria please see the study protocol).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of tepotinib in subjects with advanced adenocarcinoma of the lung harboring the MET exon 14 (METex14) skipping alterations, 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. ;Secondary Objective: To further assess the efficacy of tepotinib - To assess tolerability and safety of tepotinib - To assess PK of tepotinib and its metabolite(s) - To assess Health-Related Quality of Life (HRQoL) Exploratory Objectives -To explore a possible link between biomarkers of c-Met pathway activation, other relevant oncogenic pathways in plasma, serum and tumor tissue, and the activity of tepotinib - To explore the QT/QTc interval concentration relationship based on Cycle 1, Day 1 and Cycle 2, Day 1 data. ;Primary end point(s): Objective response rate;Timepoint(s) of evaluation of this end point: After 12 subjects have completed 4 cycles (84 days) or have prematurely discontinued trial treatment for any reason, a futility analysis will be conducted. If 3 or less confirmed responders are observed, the trial will be discontinued. The primary analysis of the trial will be conducted once all subjects have either been treated with tepotinib for at least 6 months, died or have prematurely discontinued trial treatment for any reason (following the End of Treatment Visit, if completed), whichever comes first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective response rate assessed as per Investigator 2. Duration of response as assessed by independent review committee 3. Duration of response as assessed by investigator 4. Objective disease control Rate as assessed by independent review committee 5. Objective disease control Rate as assessed by investigator 6. Progression free survival as assessed by independent review committee 7. Progression free survival as assessed by investigator 8. Overall survival 9. Number of subjects with TEAEs and deaths 10. Number of subjects with markedly abnormal vital signs, ECG, physical examination and ECOG PS. 11. Health Related Quality of Life Parameters 12. Maximum plasma concentration (Cmax) of Drug 13. Volume of distribution (Vz/F) of drug 14. Total Clearance (Cl) of drug ;Timepoint(s) of evaluation of this end point: 2, 3, 6, 7: Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months 8: Baseline until death , assessed up to 20 months 1, 4, 5, 10, 11: Baseline up to 20 months 9: From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 months 12 to 14: 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 | — |
Countries
Austria, Belgium, France, Germany, Italy, Japan, Netherlands, Poland, Spain, United States
Contacts
Public ContactCommunication Center
Merck KGaA
Outcome results
None listed