Brief Summary
MGCD265 is an orally administered receptor tyrosine kinase inhibitor that targets MET and other receptors. This study is a Phase 2 trial of MGCD265 in patients with locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC) that has activating genetic changes of the MET gene (mutation or amplification \[increase number of gene copies\]). Testing for tumor gene changes can be performed in tumor tissue or blood samples. Patients must have previously received treatment with chemotherapy. The number of patients to be enrolled will depend on how many enrolled patients experience tumor size reduction. MGCD265 will be administered orally, twice daily. The study is designed to evaluate whether the number of patients experiencing tumor size reduction is substantially higher than would be expected with other available treatments.
Brief Title
Phase 2 Study of MGCD265 in Patients With Non-Small Cell Lung Cancer With Activating Genetic Alterations in MET
Detailed Description
If testing has not already been performed, the study will provide for the testing.
Completion Date
Completion Date Type
Actual
Conditions
Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
* Diagnosis of non-small cell lung cancer
* Metastatic or locally advanced disease
* Prior platinum chemotherapy or immunotherapy
* Test result showing genetic change in MET tumor gene
* At least one tumor that can be measured on a radiographic scan
Exclusion Criteria:
* Prior treatment with inhibitor of MET or HGF
* Prior positive test for EGFR mutation or ALK gene rearrangement
* Uncontrolled tumor in the brain
* Diagnosis of non-small cell lung cancer
* Metastatic or locally advanced disease
* Prior platinum chemotherapy or immunotherapy
* Test result showing genetic change in MET tumor gene
* At least one tumor that can be measured on a radiographic scan
Exclusion Criteria:
* Prior treatment with inhibitor of MET or HGF
* Prior positive test for EGFR mutation or ALK gene rearrangement
* Uncontrolled tumor in the brain
Inclusion Criteria
Inclusion Criteria:
* Diagnosis of non-small cell lung cancer
* Metastatic or locally advanced disease
* Prior platinum chemotherapy or immunotherapy
* Test result showing genetic change in MET tumor gene
* At least one tumor that can be measured on a radiographic scan
* Diagnosis of non-small cell lung cancer
* Metastatic or locally advanced disease
* Prior platinum chemotherapy or immunotherapy
* Test result showing genetic change in MET tumor gene
* At least one tumor that can be measured on a radiographic scan
Gender
All
Gender Based
false
Keywords
Mirati
MGCD265
MET
NSCLC
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02544633
Org Class
Industry
Org Full Name
Mirati Therapeutics Inc.
Org Study Id
265-109
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Phase 2, Parallel-Arm Study of MGCD265 in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Activating Genetic Alterations in Mesenchymal-Epithelial Transition Factor
Primary Outcomes
Outcome Description
Objective disease response is defined as the percent of patients documented by investigator assessment to have a confirmed Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for target and non-target lesions as assessed by CT or MRI. CR is defined as complete disappearance of all target lesions with the exception of nodal disease; PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions; Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression; Progressive Disease (PD) is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions.
Outcome Measure
Objective Response Rate
Outcome Time Frame
Up to 3 months
Secondary Outcomes
Outcome Description
Duration of Response (DR) will be defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of Objective Progression of Disease (PD) or to death due to any cause in the absence of documented PD.
Outcome Time Frame
From date of the first documentation of objective tumor response (CR or PR) to the first documentation of Objective Progression of Disease (PD) or to death due to any cause in the absence of documented PD, assessed up to 24 months.
Outcome Measure
Duration of Response
Outcome Description
Progression-free survival (PFS) will be defined as the time from date of first study treatment to first PD or death due to any cause in the absence of documented PD. Per RECIST 1.1, Progressive Disease (PD) is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions.
Outcome Time Frame
The time from date of first study treatment to first PD or death due to any cause in the absence of documented PD, up to 24 months.
Outcome Measure
Progression Free Survival
Outcome Description
1-Year Survival will be defined as the probability of survival at 1 year after the first dose.
Outcome Time Frame
From date of first study treatment to death due to any cause, assessed up to 12 months
Outcome Measure
1-Year Survival Rate
Outcome Description
Overall Survival will be defined as the time from date of first study treatment to death due to any cause
Outcome Time Frame
From date of first study treatment to death due to any cause, assessed up to 24 months.
Outcome Measure
Overall Survival
Outcome Description
Number of patients experiencing treatment-emergent adverse events.
Outcome Time Frame
Date of first dose to 28 days after the last dose, up to an average of 5.1 months on treatment.
Outcome Measure
Number of Patients Experiencing Treatment-emergent Adverse Events
Outcome Description
Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose.
Outcome Time Frame
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Outcome Measure
Blood Plasma Concentration of MGCD265 - AUC0-6
Outcome Description
Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. On Cycle 2, samples were collected on Day 1 and Day 15 at pre-dose and at 6 hours post-dose (4-8 hours). Note: Assessment of Cmax and Tmax are limited by the sparse blood sampling schedule post dose (i.e., only 2 blood draws post-dose in Cycle 1 and only 1 sample collected post-dose in Cycle 2). The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose.
Outcome Time Frame
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. Cycle 2, Day 1 and Day 15 at pre-dose and at 6 hours post-dose (4-8 hours).
Outcome Measure
Blood Plasma Concentration of MGCD265 - Cmax
Outcome Description
Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. On Cycle 2, samples were collected on Day 1 and Day 15 at pre-dose and at 6 hours post-dose (4-8 hours). The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose.
Outcome Time Frame
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. Cycle 2, Day 1 and Day 15 at pre-dose and at 6 hours post-dose (4-8 hours).
Outcome Measure
Blood Plasma Concentration of MGCD265 - Ctrough
Outcome Description
Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose. Accumulation Ratio AUC0-6 = AUC0-6 C1D15/ AUC0-6 C1D1.
Outcome Time Frame
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Outcome Measure
Blood Plasma Concentration of MGCD265 - Accumulation Ratio AUC0-6
Outcome Description
Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose. Accumulation Ration Cmax = Cmax C1D15/ Cmax C1D1.
Outcome Time Frame
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Outcome Measure
Blood Plasma Concentration of MGCD265 - Accumulation Ratio Cmax
Outcome Description
Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose. Peak to trough ratio calculated as C1D15 Cmax/Ctrough.
Outcome Time Frame
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Outcome Measure
Blood Plasma Concentration of MGCD265 - Peak to Trough Ratio
Outcome Description
Blood samples for PK assessment were to be taken on Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose. Note: Assessment of Cmax and Tmax are limited by the sparse blood sampling schedule post dose (i.e., only 2 blood draws post-dose in Cycle 1 and only 1 sample collected post-dose in Cycle 2). The number of patients reported for each PK parameter was dependent on the actual number of blood samples collected post-dose.
Outcome Time Frame
Cycle 1, Day 1 and Day 15 at pre-dose and at 2 hours (1-3 hours) and 6 hours (4-8 hours) post-dose.
Outcome Measure
Blood Plasma Concentration of MGCD265 - Tmax
Outcome Description
Only a sub-set of patients had different molecular techniques completed, therefore a correlation analysis was not performed. Patients with positive identification by two different analytical techniques are tabulated for MET Activating Mutations.
Outcome Time Frame
At baseline
Outcome Measure
Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Activating Mutations
Outcome Description
Only a sub-set of patients had different molecular techniques completed, therefore a correlation analysis was not performed. Patients with positive identification by two different analytical techniques are tabulated for MET Gene Amplifications.
Outcome Time Frame
At baseline
Outcome Measure
Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Gene Amplifications
Outcome Time Frame
At baseline and at time of confirmation of response to treatment
Outcome Measure
Assess Change in Genetic Alteration Status in ctDNA With MGCD265 Treatment Over Time in the Selected Population
Outcome Description
MET Activating Mutations in ctDNA. Change from Baseline - Cycle 2 Day 15 - Pre-Dose Standard Deviation not evaluable
Outcome Time Frame
Cycle 1 and Cycle 2
Outcome Measure
Blood Plasma Concentration of Soluble MET (sMET) Biomarker
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES