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

Non-Small Cell Lung Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02544633
• Other study ID #: 265-109
• Status: Completed
• Phase: Phase 2
• Start date: October 2015
• Est. completion date: January 2019

Study information

• Verified date: February 2020
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: January 2019
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• MGCD265
MGCD265 is a small molecule multi-targeted receptor tyrosine kinase inhibitor

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hungary,  Italy,  Korea, Republic of,  Poland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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).
Secondary	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).
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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