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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: MGCD265

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, 5042
    • Flinders Medical Centre
  • Clayton, Australia, 3165
    • Monash Health
  • Tweed Heads, Australia, 2485
    • The Tweed Hospital
  • Woolloongabba, Australia, 4102
    • Princess Alexandra Hospital
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Kogarah, New South Wales, Australia, 2217
      • Saint George Hospital
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3165
      • Monash Cancer Centre
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
• Canada
  • Montréal, Canada, H2W 1S6
    • McGill University Health Centre
• Hungary
  • Budapest, Hungary, 1121
    • Orszagos Koranyi Tbc es Pulmonologiai Intezet
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary, 1125
    • Semmelweis Egyetem
  • Komarom-esztergom
    • Tatabánya, Komarom-esztergom, Hungary, 2800
      • Szent Borbala Korhaz
• Italy
  • Firenze, Italy, 50139
    • Azienda Ospedaliero-Universitaria Careggi
  • Lucca, Italy, 55041
    • Ospedale Unico Versilia
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20132
    • IRCCS Ospedale San Raffaele
  • Milano, Italy, 20132
    • Istituto Europeo di Oncologia Milano
  • Piacenza, Italy, 29100
    • Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto
  • Ravenna, Italy, 48121
    • Azienda Unita Sanitaria Locale Di Ravenna
  • Torino, Italy, 10126
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-712
    • Keimyung University Dongsan Medical Center
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 134-791
    • Veterans Health Service Medical Center
  • Chungcheongbuk-do
    • Cheongju, Chungcheongbuk-do, Korea, Republic of, 361-271
      • Chungbuk National University Hospital
  • Gyeonggi-do
    • Goyang, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 442-723
      • Saint Vincent Hospital
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 442-723
      • The Catholic University of Korea Saint Vincent's Hospital
• Poland
  • Pomorskie
    • Gdańsk, Pomorskie, Poland, 80-952
      • Uniwersyteckie Centrum Kliniczne
  • Warminsko-mazurskie
    • Olsztyn, Warminsko-mazurskie, Poland, 10-357
      • Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc w Olsztynie
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-693
      • Med Polonia Sp. z o.o.
• Taiwan
  • Hualien City, Taiwan, 970
    • Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Tainan
    • Tainan City, Tainan, Taiwan, 73657
      • Chi Mei Hospital Liouying
  • Tainan CITY
    • Tainan, Tainan CITY, Taiwan, 70403
      • National Cheng Kung University
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free London NHS Foundation Trust
  • England
    • Bristol, England, United Kingdom, BS10 5NB
      • North Bristol NHS Trust, Westbury on Trym
    • London, England, United Kingdom, NW1 2PQ
      • University College London Hospitals NHS Foundation Trust
    • Northwood, England, United Kingdom, HA6 2RN
      • East and North Hertordshire NHS Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Huntsville, Alabama, United States, 35805
      • Clearview Cancer Institute
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Fowler Family Center for Cancer Care
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center
    • Fullerton, California, United States, 92835-3825
      • Saint Joseph Heritage Healthcare
    • La Jolla, California, United States, 92121
      • University of California San Diego
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • Whittier, California, United States, 90603
      • Innovative Clinical Reseach Institute
  • Colorado
    • Grand Junction, Colorado, United States, 81501
      • St. Mary's Regional Cancer Center
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology Associates
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital - Eugene M. & Christine E. Lynn Cancer Institute
    • Deerfield Beach, Florida, United States, 33442-7753
      • Sylvester Comprehensive Cancer Center
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Hospital West
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
    • Evanston, Illinois, United States, 60201
      • Northshore University Healthsystem
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Goshen Center for Cancer Care
  • Iowa
    • Mason City, Iowa, United States, 50401
      • Mercy Cancer Center
  • Kentucky
    • Danville, Kentucky, United States, 40422-2534
      • Oncology-Hematology Associates, PA
    • Lexington, Kentucky, United States, 40503
      • Lexington Oncology Associates, LLC
    • Louisville, Kentucky, United States, 40245
      • Kentuckyone Health Cancer and Blood Speacialists
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Christus Saint Frances Cabrini Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Masonic Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • The University of New Mexico Cancer Research and Treatment Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Jamaica, New York, United States, 11430
      • Queens Cancer Center
    • New York, New York, United States, 10021
      • Clinical Research Alliance
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Of Cleveland
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 752010
      • Mary Crowley Cancer Research Centers
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	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.	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response	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.	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.
Progression Free Survival	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.	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.
1-Year Survival Rate	1-Year Survival will be defined as the probability of survival at 1 year after the first dose.	From date of first study treatment to death due to any cause, assessed up to 12 months
Overall Survival	Overall Survival will be defined as the time from date of first study treatment to death due to any cause	From date of first study treatment to death due to any cause, assessed up to 24 months.
Number of Patients Experiencing Treatment-emergent Adverse Events	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.
Blood Plasma Concentration of MGCD265 - AUC0-6	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.	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 Plasma Concentration of MGCD265 - Cmax	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.	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 Plasma Concentration of MGCD265 - Ctrough	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.	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 Plasma Concentration of MGCD265 - Accumulation Ratio AUC0-6	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.	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 Plasma Concentration of MGCD265 - Accumulation Ratio Cmax	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.	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 Plasma Concentration of MGCD265 - Peak to Trough Ratio	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.	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 Plasma Concentration of MGCD265 - Tmax	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.	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.
Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Activating Mutations	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.	At baseline
Assess Correlation Between Selected Tumor Gene Alterations Using Different Analytical Techniques in Tumor Tissue and Circulating Tumor Deoxyribonucleic Acid (ctDNA) - MET Gene Amplifications	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.	At baseline
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
Blood Plasma Concentration of Soluble MET (sMET) Biomarker	MET Activating Mutations in ctDNA. Change from Baseline - Cycle 2 Day 15 - Pre-Dose Standard Deviation not evaluable	Cycle 1 and Cycle 2

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): April 30, 2018
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: September 4, 2015
• First Submitted That Met QC Criteria: September 4, 2015
• First Posted (Estimate): September 9, 2015

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: NSCLC; MET; Mirati; MGCD265
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 265-109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO