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

Phase 2

Completed

Conditions: Non-Small Cell Lung Cancer

Interventions: Drug: MGCD265

Registration Number: NCT02544633

Lead Sponsor: Mirati Therapeutics Inc.

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.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 68

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 3	MGCD265	MGCD265 in patients with MET activating mutations in blood (circulating tumor DNA)
Arm 4	MGCD265	MGCD265 in patients with MET gene amplifications in blood (circulating tumor DNA)
Arm 1	MGCD265	MGCD265 in patients with MET activating mutations in tumor tissue
Arm 2	MGCD265	MGCD265 in patients with MET gene amplifications in tumor tissue

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	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

Name	Time	Method
Blood Plasma Concentration of MGCD265 - Accumulation Ratio Cmax	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.
Blood Plasma Concentration of MGCD265 - Peak to Trough Ratio	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.
Blood Plasma Concentration of MGCD265 - Tmax	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.
Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Activating Mutations	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.
Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Gene Amplifications	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.
Blood Plasma Concentration of Soluble MET (sMET) Biomarker	Cycle 1 and Cycle 2	MET Activating Mutations in ctDNA. Change from Baseline - Cycle 2 Day 15 - Pre-Dose Standard Deviation not evaluable
Duration of Response	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.
Progression Free Survival	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.
1-Year Survival Rate	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.
Overall Survival	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
Number of Patients Experiencing Treatment-emergent Adverse Events	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.
Blood Plasma Concentration of MGCD265 - AUC0-6	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.
Blood Plasma Concentration of MGCD265 - Cmax	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.
Blood Plasma Concentration of MGCD265 - Ctrough	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.
Blood Plasma Concentration of MGCD265 - Accumulation Ratio AUC0-6	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.
Assess Change in Genetic Alteration Status in ctDNA With MGCD265 Treatment Over Time in the Selected Population	At baseline and at time of confirmation of response to treatment

Trial Locations

Locations (93): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Clearview Cancer Institute
🇺🇸
Huntsville, Alabama, United States
Fowler Family Center for Cancer Care
🇺🇸
Jonesboro, Arkansas, United States
Providence Saint Joseph Medical Center
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Burbank, California, United States
Saint Joseph Heritage Healthcare
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Fullerton, California, United States
University of California San Diego
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La Jolla, California, United States
Loma Linda University Medical Center
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Loma Linda, California, United States
University of California, San Francisco
🇺🇸
San Francisco, California, United States
Innovative Clinical Reseach Institute
🇺🇸
Whittier, California, United States
St. Mary's Regional Cancer Center
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Grand Junction, Colorado, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States