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Phase 2 Study of MGCD265 in Patients With Non-Small Cell Lung Cancer With Activating Genetic Alterations in MET

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ClinicalTrials.gov Identifier: NCT02544633
Recruitment Status : Completed
First Posted : September 9, 2015
Results First Posted : September 10, 2019
Last Update Posted : March 4, 2020
Sponsor:
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: MGCD265 Phase 2

Detailed Description:
If testing has not already been performed, the study will provide for the testing.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : October 2015
Actual Primary Completion Date : April 30, 2018
Actual Study Completion Date : January 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1
MGCD265 in patients with MET activating mutations in tumor tissue
 Drug: MGCD265
MGCD265 is a small molecule multi-targeted receptor tyrosine kinase inhibitor
Experimental: Arm 2
MGCD265 in patients with MET gene amplifications in tumor tissue
 Drug: MGCD265
MGCD265 is a small molecule multi-targeted receptor tyrosine kinase inhibitor
Experimental: Arm 3
MGCD265 in patients with MET activating mutations in blood (circulating tumor DNA)
 Drug: MGCD265
MGCD265 is a small molecule multi-targeted receptor tyrosine kinase inhibitor
Experimental: Arm 4
MGCD265 in patients with MET gene amplifications in blood (circulating tumor DNA)
 Drug: MGCD265
MGCD265 is a small molecule multi-targeted receptor tyrosine kinase inhibitor


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: Up to 3 months ]
    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.


Secondary Outcome Measures :
  1. Duration of Response [ 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. ]
    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.

  2. Progression Free Survival [ 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. ]
    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.

  3. 1-Year Survival Rate [ Time Frame: From date of first study treatment to death due to any cause, assessed up to 12 months ]
    1-Year Survival will be defined as the probability of survival at 1 year after the first dose.

  4. Overall Survival [ Time Frame: From date of first study treatment to death due to any cause, assessed up to 24 months. ]
    Overall Survival will be defined as the time from date of first study treatment to death due to any cause

  5. Number of Patients Experiencing Treatment-emergent Adverse Events [ Time Frame: Date of first dose to 28 days after the last dose, up to an average of 5.1 months on treatment. ]
    Number of patients experiencing treatment-emergent adverse events.

  6. Blood Plasma Concentration of MGCD265 - AUC0-6 [ 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. ]
    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.

  7. Blood Plasma Concentration of MGCD265 - Cmax [ 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). ]
    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.

  8. Blood Plasma Concentration of MGCD265 - Ctrough [ 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). ]
    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.

  9. Blood Plasma Concentration of MGCD265 - Accumulation Ratio AUC0-6 [ 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. ]
    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.

  10. Blood Plasma Concentration of MGCD265 - Accumulation Ratio Cmax [ 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. ]
    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.

  11. Blood Plasma Concentration of MGCD265 - Peak to Trough Ratio [ 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. ]
    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.

  12. Blood Plasma Concentration of MGCD265 - Tmax [ 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. ]
    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.

  13. Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Activating Mutations [ Time Frame: At baseline ]
    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.

  14. Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Gene Amplifications [ Time Frame: At baseline ]
    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.

  15. Assess Change in Genetic Alteration Status in ctDNA With MGCD265 Treatment Over Time in the Selected Population [ Time Frame: At baseline and at time of confirmation of response to treatment ]
  16. Blood Plasma Concentration of Soluble MET (sMET) Biomarker [ Time Frame: Cycle 1 and Cycle 2 ]
    MET Activating Mutations in ctDNA. Change from Baseline - Cycle 2 Day 15 - Pre-Dose Standard Deviation not evaluable


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02544633


Locations
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Sponsors and Collaborators
Mirati Therapeutics Inc.
  Study Documents (Full-Text)

Documents provided by Mirati Therapeutics Inc.:
Study Protocol and Statistical Analysis Plan  [PDF] March 23, 2017

More Information
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Responsible Party: Mirati Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT02544633    
Other Study ID Numbers: 265-109
First Posted: September 9, 2015    Key Record Dates
Results First Posted: September 10, 2019
Last Update Posted: March 4, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Mirati Therapeutics Inc.:
Mirati
MGCD265
MET
NSCLC
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms