Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Adagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04330664
Recruitment Status : Active, not recruiting
First Posted : April 1, 2020
Last Update Posted : November 22, 2021
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation.

Condition or disease Intervention/treatment Phase
Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease Drug: MRTX849 Drug: TNO155 Phase 1 Phase 2

Detailed Description:
This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric inhibitor of wild-type SHP2.
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2
Actual Study Start Date : April 22, 2020
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Phase 1 Dose Exploration
Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849
 Drug: MRTX849
KRAS G12C Inhibitor
Other Name: adagrasib

Drug: TNO155
SHP2 Inhibitor
Experimental: Phase 1b Expansion
Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens
 Drug: MRTX849
KRAS G12C Inhibitor
Other Name: adagrasib

Drug: TNO155
SHP2 Inhibitor
Experimental: Phase 2
Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination
 Drug: MRTX849
KRAS G12C Inhibitor
Other Name: adagrasib

Drug: TNO155
SHP2 Inhibitor


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation. [ Time Frame: 20 months ]
    Number of participants with treatment related adverse events

  2. Evaluate the pharmacokinetics of MRTX849 and TNO155 [ Time Frame: 20 months ]
    Blood plasma concentration


Secondary Outcome Measures :
  1. Establish maximum tolerated dose [ Time Frame: 12 months ]
    Number of participants with dose limiting toxicity

  2. Evaluate clinical activity of MRTX849 [ Time Frame: 20 months ]
    Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer)
  • Unresectable or metastatic disease
  • No available treatment with curative intent
  • Adequate organ function

Exclusion Criteria:

  • History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
  • Other active cancer
  • Cardiac abnormalities
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04330664


Locations
Layout table for location information
United States, California
UCLA Jonsson Comprehensive Cancer Center
Los Angeles, California, United States, 90095
UC Irvine Health
Orange, California, United States, 92868
United States, Illinois
Northwestern
Chicago, Illinois, United States, 60611
United States, Kansas
Cancer Center of Kansas
Wichita, Kansas, United States, 67214
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University School of Medicine Siteman Cancer Center
Saint Louis, Missouri, United States, 63110
United States, New York
NYU Perlmutter Cancer Center
New York, New York, United States, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, Texas
NEXT Oncology
San Antonio, Texas, United States, 78229
United States, Wisconsin
Froedtert Hospital & Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Mirati Therapeutics Inc.
Novartis
Investigators
Layout table for investigator information
Study Director: Elise Walsh, MD Mirati Therapeutics Inc.
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Mirati Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04330664    
Other Study ID Numbers: 849-002
First Posted: April 1, 2020    Key Record Dates
Last Update Posted: November 22, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mirati Therapeutics Inc.:
KRAS G12C
Non-small cell lung cancer
Colorectal Cancer
Colon Cancer
Metastatic Cancer
 Pancreatic Cancer
NSCLC
SHP2
Advanced Solid Tumors
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
 Pathologic Processes
Adagrasib
Antineoplastic Agents