Phase 2 Study of MGCD265 in Patients With Non-Small Cell Lung Cancer With Activating Genetic Alterations in MET
- 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
- 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
- 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.
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 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.
Trial Locations
- Locations (93)
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Eastern Connecticut Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Fowler Family Center for Cancer Care
🇺🇸Jonesboro, Arkansas, United States
Guthrie Cancer Center
🇺🇸Sayre, Pennsylvania, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Saint Joseph Heritage Healthcare
🇺🇸Fullerton, California, United States
Clearview Cancer Institute
🇺🇸Huntsville, Alabama, United States
Providence Saint Joseph Medical Center
🇺🇸Burbank, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Boca Raton Regional Hospital - Eugene M. & Christine E. Lynn Cancer Institute
🇺🇸Boca Raton, Florida, United States
Innovative Clinical Reseach Institute
🇺🇸Whittier, California, United States
St. Mary's Regional Cancer Center
🇺🇸Grand Junction, Colorado, United States
Sylvester Comprehensive Cancer Center
🇺🇸Deerfield Beach, Florida, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
Florida Cancer Specialists
🇺🇸Saint Petersburg, Florida, United States
Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
NorthShore University HealthSystem
🇺🇸Evanston, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Mercy Cancer Center
🇺🇸Mason City, Iowa, United States
Oncology-Hematology Associates, PA
🇺🇸Danville, Kentucky, United States
Lexington Oncology Associates, LLC
🇺🇸Lexington, Kentucky, United States
Christus Saint Frances Cabrini Hospital
🇺🇸Alexandria, Louisiana, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The University of New Mexico Cancer Research and Treatment Center
🇺🇸Albuquerque, New Mexico, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Queens Cancer Center
🇺🇸Jamaica, New York, United States
Clinical Research Alliance
🇺🇸New York, New York, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Greenville Health System
🇺🇸Greenville, South Carolina, United States
Mary Crowley Cancer Research Centers
🇺🇸Dallas, Texas, United States
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Saint George Hospital
🇦🇺Kogarah, New South Wales, Australia
Royal North Shore Hospital
🇦🇺Saint Leonards, New South Wales, Australia
Monash Cancer Centre
🇦🇺Clayton, Victoria, Australia
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Monash Health
🇦🇺Clayton, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
The Tweed Hospital
🇦🇺Tweed Heads, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Australia
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
🇨🇳Hualien City, Taiwan
Istituto Europeo di Oncologia Milano
🇮🇹Milano, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Országos Onkológiai Intézet
ðŸ‡ðŸ‡ºBudapest, Hungary
Szent Borbála Kórház
ðŸ‡ðŸ‡ºTatabánya, Komarom-esztergom, Hungary
Azienda Ospedaliero-Universitaria Careggi
🇮🇹Firenze, Italy
Ospedale Unico Versilia
🇮🇹Lucca, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto
🇮🇹Piacenza, Italy
Azienda Unita Sanitaria Locale di Ravenna
🇮🇹Ravenna, Italy
Országos Korányi TBC és Pulmonológiai Intézet
ðŸ‡ðŸ‡ºBudapest, Hungary
Chungbuk National University Hospital
🇰🇷Cheongju, Chungcheongbuk-do, Korea, Republic of
Semmelweis Egyetem
ðŸ‡ðŸ‡ºBudapest, Hungary
McGill University Health Centre
🇨🇦Montréal, Canada
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹Torino, Italy
National Cancer Center
🇰🇷Goyang, Gyeonggi-do, Korea, Republic of
Saint Vincent Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
The Catholic University of Korea Saint Vincent's Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Pomorskie, Poland
Med Polonia Sp. z o.o.
🇵🇱Poznan, Wielkopolskie, Poland
National Cheng Kung University
🇨🇳Tainan, Tainan CITY, Taiwan
Chi Mei Hospital Liouying
🇨🇳Tainan City, Tainan, Taiwan
Veterans Health Service Medical Center
🇰🇷Seoul, Korea, Republic of
Samodzielny Publiczny Zespól Gruzlicy i Chorób Pluc w Olsztynie
🇵🇱Olsztyn, Warminsko-mazurskie, Poland
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
East and North Hertordshire NHS Trust
🇬🇧Northwood, England, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧London, England, United Kingdom
North Bristol NHS Trust, Westbury on Trym
🇬🇧Bristol, England, United Kingdom
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of Minnesota Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Kentuckyone Health Cancer and Blood Speacialists
🇺🇸Louisville, Kentucky, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom