Tepotinib Phase II Study in NSCLC Harboring MET Exon 14 (METex14) Skipping Alterations or MET amplificatio
- Conditions
- advanced (Stage IIIB/IV) non-small cell lung cancer
- Registration Number
- JPRN-jRCT2080223315
- Lead Sponsor
- Merck Biopharma Co., Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 120
Histologically confirmed advanced (Stage IIIB/IV) NSCLC (all histologies including squamous and sarcomatoid)
-Treatment naive patients in first-line or pretreated patients with no more than 2 lines of prior therapy
-METex14 skipping alterations in plasma and/or tissue, as determined by the central laboratory or by an assay with appropriate regulatory status will, be enrolled into the trial.
For these subjects, sufficient tumor tissue and/or plasma is requested to allow additional testing
-MET amplification only in plasma defined by a positive LBx test, as determined by the central laboratory or by an assay with appropriate regulatory status
-Based on the outcome of the interim analysis in 12 LBx selected subjects: MET amplification only in tissue defined by a positive TBx with a gain of at least 4 copies of the MET gene, as determined by the central laboratory or by an assay with appropriate regulatory status.
-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 than 18 years of age)
-Measurable disease in accordance with RECIST version 1.1
-ECOG PS of 0 or 1
-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 (<=) 1cm of longest diameter are eligible
-Any unresolved toxicity Grade 2 or more according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03, from previous anticancer therapy
-Need for transfusion within 14 days prior to the first dose of trial treatment
-Subjects with characterized EGFR activating mutations that predict sensitivity to anti-EGFR therapy
-Subjects with characterized ALK rearrangements that predict sensitivity to anti-ALK therapy
-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
-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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method efficacy<br>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 CR or 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
Name Time Method safety<br>efficacy<br>pharmacokinetics<br>Objective response assessed as per Investigator<br>Duration of response<br>Objective disease control<br>Progression free survival<br>Overall survival<br>Safety Information<br>QOL(EORTC QLQ-C30,EORTC QLQ-LC13,EQ5D5L)<br>Pharmacokinetics