Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1

Metastatic Cancer Clinical Trial

Official title:

A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03785249
• Other study ID #: CA239-0008
• Secondary ID: CA239-0008849-00
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 26, 2018
• Est. completion date: January 31, 2026

Study information

• Verified date: June 2024
• Source: Mirati Therapeutics Inc.
• Contact: BMS Clinical Trials Contact Center www.BMSClinicalTrials.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.

Description:

This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 822
• Est. completion date: January 31, 2026
• Est. primary completion date: July 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation

• Unresectable or metastatic disease

• Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts

• Adequate organ function

Exclusion Criteria:

• History of intestinal disease or major gastric surgery or inability to swallow oral medications

• Other active cancer

Related Conditions & MeSH terms

• Advanced Cancer
• Malignant Neoplastic Disease
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms

Intervention

Drug:
• MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen
• Pembrolizumab
Pembrolizumab is administered as an intravenous infusion once every 3 weeks
• Cetuximab
Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
• Afatinib
Afatinib will be administered orally once a day in a continuous regimen

Locations

Country	Name	City	State
Puerto Rico	PanOncology Trials - Rio Piedras Medical Center	San Juan
United States	New York Oncology Hematology - Albany Medical Center	Albany	New York
United States	Lehigh Valley Physician Group Hematology Oncology	Allentown	Pennsylvania
United States	Alaska Oncology and Hematology	Anchorage	Alaska
United States	USOR - Texas Oncology Dallas Fort Worth West (DFWW) - Arlington South	Arlington	Texas
United States	University Cancer & Blood Center (UCBC) - Athens	Athens	Georgia
United States	Local Institution - 001-872	Aurora	Colorado
United States	UCHealth Cancer Care - Anschutz Medical Campus - University of Colorado Cancer Center	Aurora	Colorado
United States	USOR - Texas Oncology - Austin Central	Austin	Texas
United States	SCRI - Hematology Oncology Clinic - Baton Rouge	Baton Rouge	Louisiana
United States	St. Charles Health System	Bend	Oregon
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	MaineHealth Cancer Care - Biddeford	Biddeford	Maine
United States	Sisters of Charity of Leavenworth Health St. Marys	Billings	Montana
United States	ONeal Comprehensive Cancer Center at the University of Alabama at Birmingham	Birmingham	Alabama
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	USOR - Charleston Hematology Oncology Associates	Charleston	South Carolina
United States	Local Institution - 001-828	Chicago	Illinois
United States	Affiliated Oncologists - Millenium Medical Center - Chicago Ridge	Chicago Ridge	Illinois
United States	The Christ Hospital	Cincinnati	Ohio
United States	University of Cincinnati Health Barrett Cancer Center	Cincinnati	Ohio
United States	Cleveland Clinic Lerner College of Medicine	Cleveland	Ohio
United States	Maryland Oncology Hematology - Columbia	Columbia	Maryland
United States	SCRI - Mark H. Zangmeister Cancer Center	Columbus	Ohio
United States	The Ohio State University College of Medicine	Columbus	Ohio
United States	Mary Crowley Cancer Research - Medical City Hospital	Dallas	Texas
United States	USOR - Texas Oncology - Dallas Fort Worth (DFW) - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	USOR - Texas Oncology - Dallas Fort Worth (DFW) - Presbyterian Cancer Center Dallas	Dallas	Texas
United States	USOR - Texas Oncology Northeast Texas - Denison	Denison	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope - Duarte (Main Campus)	Duarte	California
United States	Willamette Valley Cancer Institute and Research Center - Eugene	Eugene	Oregon
United States	Local Institution - 001-919	Fairfax	Virginia
United States	NEXT Virginia	Fairfax	Virginia
United States	SCRI - Florida Cancer Specialists - South Region Research Office	Fort Myers	Florida
United States	Texas Oncology - Dallas Fort Worth (DFW) - Fort Worth	Fort Worth	Texas
United States	Hematology Oncology Associates of Fredericksburg	Fredericksburg	Virginia
United States	Providence Medical Foundation - Virginia K. Crosson Cancer Center - Fullerton	Fullerton	California
United States	Cancer Centers of Colorado - St. Marys Regional Hospital	Grand Junction	Colorado
United States	USOR - Comprehensive Cancer Centers of Nevada - Southeast Henderson	Henderson	Nevada
United States	Penn State Cancer Institute	Hershey	Pennsylvania
United States	Oncology Consultants - Texas Medical Center	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Local Institution - 001-831	Iowa City	Iowa
United States	Local Institution - 001-999	Irving	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Kettering Health Cancer Center - Main Campus	Kettering	Ohio
United States	Lumi Research	Kingwood	Texas
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	SCL Health - Saint Joseph Hospital Cancer Center	Lafayette	Colorado
United States	Local Institution - 001-832	Lake Success	New York
United States	Cancer Centers of Southwest Oklahoma - Leah M. Fitch Cancer Center	Lawton	Oklahoma
United States	University of Kentucky	Lexington	Kentucky
United States	TRIO - Cancer and Blood Specialty Clinic	Los Alamitos	California
United States	Southern California Permanente Medical Group - Los Angeles Medical Center	Los Angeles	California
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	University Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Northwest Georgia Oncology Centers Wellstar - Marietta	Marietta	Georgia
United States	USOR - Alliance Cancer Specialists - Media (Cancer Center at Riddle Memorial Hospital)	Media	Pennsylvania
United States	Miami Cancer Institute	Miami	Florida
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	USOR - Texas Oncology - Midland Allison Cancer Center	Midland	Texas
United States	Masonic Cancer Center	Minneapolis	Minnesota
United States	USOR - Minnesota Oncology - Minneapolis Clinic	Minneapolis	Minnesota
United States	Tennessee Oncology - Nashville - Centennial Clinic - Medical Oncology	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Local Institution - 001-583	New York	New York
United States	Memorial Sloan Kettering Cancer Center - New York	New York	New York
United States	Perlmutter Cancer Center - 34th Street	New York	New York
United States	USOR - Medical Oncology Hematology Consultants	Newark	Delaware
United States	Hoag Memorial Hospital Presbyterian - Newport Beach	Newport Beach	California
United States	USOR - Virginia Oncology Associates - Newport News	Newport News	Virginia
United States	USOR - Illinois Cancer Specialists - Niles	Niles	Illinois
United States	Florida Cancer Affiliates - Ocala - Main	Ocala	Florida
United States	Local Institution - 001-580	Oklahoma City	Oklahoma
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of California Irvine Medical Center	Orange	California
United States	Mid Florida Cancer Centers - Orange City	Orange City	Florida
United States	Woodlands Medical Specialists	Pensacola	Florida
United States	Mayo Clinic Arizona - Phoenix Campus	Phoenix	Arizona
United States	FirstHealth Outpatient Cancer Center	Pinehurst	North Carolina
United States	Virginia Cancer Institute - West End	Richmond	Virginia
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Metro-Minnesota Community Oncology Research Consortium (MMCORC)	Saint Louis Park	Minnesota
United States	SCRI - Florida Cancer Specialists - North Region Research Office	Saint Petersburg	Florida
United States	START Center for Cancer Care	San Antonio	Texas
United States	California Cancer Associates for Research and Excellence (cCARE) - San Diego 4S Ranch	San Diego	California
United States	Ridley - Tree Cancer Center - Santa Barbara	Santa Barbara	California
United States	Local Institution - 001-807	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Memorial Hospital	South Bend	Indiana
United States	Texas Oncology - Sugar Land	Sugar Land	Texas
United States	USOR - Arizona Oncology - Tucson - Rudasill	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute (OCSRI) - Tulsa	Tulsa	Oklahoma
United States	Texas Oncology - Northeast Texas Cancer and Research Institute - Tyler	Tyler	Texas
United States	Kaiser Permanente - Vallejo Medical Center	Vallejo	California
United States	USOR - Northwest Cancer Specialists, P.C. dba Compass Oncology - Vancouver Cancer Center	Vancouver	Washington
United States	Texas Oncology - Waco	Waco	Texas
United States	SCRI - Florida Cancer Specialists - East Region Research Office	West Palm Beach	Florida
United States	University of Kansas Medical Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation	Number of participants with treatment related adverse events	20 months
Primary	Evaluate the pharmacokinetics of MRTX849	Blood plasma concentration	20 months
Primary	Evaluate clinical activity/efficacy of MRTX849	Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)	20 months
Secondary	Establish maximum tolerated dose	Number of participants with dose limiting toxicity	12 months
Secondary	Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents	Number of participants with dose limiting toxicity	12 months
Secondary	Evaluate the pharmacokinetics of new MRTX849 oral formulations	Blood plasma concentration	6 months
Secondary	Evaluate the pharmacokinetics of MRTX849 administered with food	Blood plasma concentration	6 months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting