MET Amplification, MET Exon 14 Skipping Mutation, Solid Tumor
Conditions
Keywords
solid tumors, MET Exon 14, MET Amplification, cMET, lung, neoplasm, cMET amplification, METex14, cancer, MET Exon 14 skipping
Brief summary
The aim of this study is to understand efficacy of tepotinib in patients with solid cancers harbouring c-MET amplification or exon 14 mutation who progressed after standard treatment for metastatic disease.
Detailed description
This study is a basket trial with two strata(NSCLC and other cancer). If MET exon 14 skipping mutation or MET amplification(copy number gain ≥6.0 ) is detected by NGS method, then confirmation of genetic findings by Molecular Steering Committee will be followed. Patient can participate in this trial after confirmation of genetic analysis and reviewing other inclusion/exclusion criteria.
Interventions
DRUGTepotinib
Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily
Sponsors
Merck KGaA, Darmstadt, Germany
Chungbuk National University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Experimental: Arm 1\_NSCLC Patients with non-small cell lung cancer (NSCLC) harboring MET alteration Experimental: Arm 2\_Other solid tumors Solid tumors excluding NSCLC harboring MET alteration
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed solid cancers (NSCLC, gastric cancer, colorectal cancer, breast cancer, hepatocellular cancer, head and neck cancer, RCC and other solid cancers) 2. Subjects who are not eligible for surgical and/or local-regional therapies or who have progressive disease (PD) after surgical and/or local-regional therapies 3. Subjects who have disease progression or are intolerant to the prior standard treatment for advanced solid cancers 4. A tumor biopsy (excluding fine needle aspiration and cytology samples) is required for determining MET status (a fresh pretreatment tumor biopsy is recommended but archived tumor sample is acceptable). 5. Patients with MET exon 14 skipping mutation detected by NGS method and c-MET copy number gain (≥6.0) in the archival or fresh tumor tissue specimen identified in K-MASTER panel. All genetic findings must be reviewed by the study Molecular Steering Committee, prior to study entry. 6. Male or female, 19 years of age or older 7. Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). The target lesion that has received previous local therapy should not be considered as measurable unless clear progression has been documented since the therapy. 8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 9. Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment 10. Life expectancy judged by the Investigator of at least 3 months
Exclusion criteria
1\. Eligibility criteria: 1. Histologically or cytologically confirmed solid cancers (NSCLC, gastric cancer, colorectal cancer, breast cancer, hepatocellular cancer, head and neck cancer, RCC and other solid cancers) 2. Subjects who are not eligible for surgical and/or local-regional therapies or who have progressive disease (PD) after surgical and/or local-regional therapies 3. Subjects who have disease progression or are intolerant to the prior standard treatment for advanced solid cancers 4. A tumor biopsy (excluding fine needle aspiration and cytology samples) is required for determining MET status (a fresh pretreatment tumor biopsy is recommended but archived tumor sample is acceptable). 5. Patients with MET exon 14 skipping mutation detected by NGS method and c-MET copy number gain (≥6.0) in the archival or fresh tumor tissue specimen identified in K-MASTER panel. All genetic findings must be reviewed by the study Molecular Steering Committee, prior to study entry. 6. Male or female, 19 years of age or older 7. Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). The target lesion that has received previous local therapy should not be considered as measurable unless clear progression has been documented since the therapy. 8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 9. Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment 10. Life expectancy judged by the Investigator of at least 3 months 2\.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rates (RECIST1.1) | Baseline up to 20 months | Objective response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator. 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
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months | Progression free survival as assessed by investigators 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 |
| Disease control rate | Baseline up to 20 months | 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. |
| Overall survival | Baseline until death, assessed up to 20 months | Overall survival is defined as the time (in months) from first trial treatment administration to the date of death. |
| Toxicity and drug compliance | From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 Months | This outcome measure will be presented as the percentage of subjects with any adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator. |
Countries
South Korea
Contacts
Primary ContactKi Hyeong Lee, M.D.
Backup ContactEun Joo Kang, M.D.
Outcome results
None listed