Patient case: 48-year-old male with Lung adenocarcinoma. Genetic variant: MET Amplification. Other conditions: Emphysema.

Clinical trial: Tepotinib Phase II Study in Lung Adenocarcinoma Harbouring MET Exon 14 (METex14) Skipping Alterations

Summary: This study will look at how effective the study drug (tepotinib) is at stopping the growth and spread of lung cancer that carries a specific genetic alteration (MET exon 14 skipping alterations) and that did not respond to standard of care treatment such as chemotherapy (platinum doublet containing regimen). 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


Eligibility: Inclusion Criteria:
  -  Histologically confirmed advanced adenocarcinoma of the lung, having failed at least one bot not more than 2 lines of systemic therapy, including a platinum-doublet-containing regimen, but having failed a maximum of 2 lines of active therapy
  -  MET Exon 14 (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
  -  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, if the age of majority is > 18 years of age); [i.e. >= 20 years of age in Japan])
  -  Measurable disease in accordance with RECIST version 1.1
  -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  -  A female subjects 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 as defined in Appendix VIII OR
  -  A woman of childbearing potential who agrees to use a highly effective contraception (i.e., methods with a failure rate of less than 1 % per year) as detailed in in Appendix VII 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 enrollment.
  -  A male subject must agree to use and to have their female partners of childbearing potential to use a highly effective contraception (i.e., methods with a failure rate of less than 1 % per year) as detailed in Appendix VII 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.
  Exclusion Criteria:
  -  Subjects with characterized Epidermal Growth Factor Receptor (EGFR) (documented results; local testing acceptable) that predict sensitivity to EGFR-therapy, including, but not limited to exon 19 deletions and exon 21 alterations
  -  Subjects with characterized Anaplastic Lymphoma Kinase (ALK) rearrangements (documented results; local testing acceptable)
  -  Active brain metastases (defined as neurologically stable for less than (<) 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 less than or equal to (<=) 1 cm are eligible
  -  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, 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 measureable lesion
  -  Inadequate hematological, liver, renal, cardiac function
  -  Prior treatment with other agents targeting the HGF/c-Met pathway
  -  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

Relevance to patient case: possibly relevant