SHS_492340 WESH CEMS 16141

A Phase II Single-Arm Trial to Investigate Tepotinib in Stage IIIB/IV Adenocarcinoma of the Lung with MET Exon 14 (METex14) Skipping Alterations After Failure of at Least One Prior Active Therapy, Including a Platinum-Doublet-Containing Regimen

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).

Inclusion Criteria:
•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
•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)
•Measurable disease in accordance with RECIST version 1.1
•ECOG PS of 0 or 1

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
•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
Phase II
Cancer, All Other
Howard (Jack) West, M.D.
EMD Serono
Andrew Smith
  • Swedish Medical Center