Clinical Trials /

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

NCT02544633

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT02544633

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 265-109
  • NCT ID: NCT02544633

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
MGCD265Arm 1

Purpose

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.

Detailed Description

      If testing has not already been performed, the study will provide for the testing.

Trial Arms

NameTypeDescriptionInterventions
Arm 1ExperimentalMGCD265 in patients with MET activating mutations in tumor tissue
  • MGCD265
Arm 2ExperimentalMGCD265 in patients with MET gene amplifications in tumor tissue
  • MGCD265
Arm 3ExperimentalMGCD265 in patients with MET activating mutations in blood (circulating tumor DNA)
  • MGCD265
Arm 4ExperimentalMGCD265 in patients with MET gene amplifications in blood (circulating tumor DNA)
  • MGCD265

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
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:Up to 3 months
Safety Issue:
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.

Secondary Outcome Measures

Measure: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.
Safety Issue:
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.
Measure: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.
Safety Issue:
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.
Measure:1-Year Survival Rate
Time Frame:From date of first study treatment to death due to any cause, assessed up to 12 months
Safety Issue:
Description:1-Year Survival will be defined as the probability of survival at 1 year after the first dose.
Measure:Overall Survival
Time Frame:From date of first study treatment to death due to any cause, assessed up to 24 months.
Safety Issue:
Description:Overall Survival will be defined as the time from date of first study treatment to death due to any cause
Measure: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.
Safety Issue:
Description:Number of patients experiencing treatment-emergent adverse events.
Measure: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.
Safety Issue:
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.
Measure: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).
Safety Issue:
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.
Measure: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).
Safety Issue:
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.
Measure: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.
Safety Issue:
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.
Measure: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.
Safety Issue:
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.
Measure: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.
Safety Issue:
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.
Measure: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.
Safety Issue:
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.
Measure: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
Safety Issue:
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.
Measure: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
Safety Issue:
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.
Measure: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
Safety Issue:
Description:
Measure:Blood Plasma Concentration of Soluble MET (sMET) Biomarker
Time Frame:Cycle 1 and Cycle 2
Safety Issue:
Description:MET Activating Mutations in ctDNA. Change from Baseline - Cycle 2 Day 15 - Pre-Dose Standard Deviation not evaluable

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Mirati Therapeutics Inc.

Trial Keywords

  • Mirati
  • MGCD265
  • MET
  • NSCLC

Last Updated

March 4, 2020