Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03785249
Recruitment Status : Recruiting
First Posted : December 24, 2018
Last Update Posted : January 9, 2023
Sponsor:
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 (adagrasib) 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: Pembrolizumab Drug: Cetuximab Drug: Afatinib Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Detailed 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.
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)
Estimated Enrollment : 822 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1
Actual Study Start Date : January 15, 2019
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : September 2024

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 MRTX849 to determine maximum tolerated dose
 Drug: MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental: Phase 1b Expansion
Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens
 Drug: MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental: Phase 2
Separate cohorts of patients stratified by histological diagnosis, prior treatment history or co-mutation status (e.g., STK11) for evaluation of clinical activity of MRTX849
 Drug: MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental: Pilot Phase 1b Combination with Pembrolizumab
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC
 Drug: MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen

Drug: Pembrolizumab
Pembrolizumab is administered as an intravenous infusion once every 3 weeks
Experimental: Pilot Phase 1b Combination with Cetuximab
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC
 Drug: MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen

Drug: Cetuximab
Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental: Pilot Phase 1b Combination with Afatinib
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC
 Drug: MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen

Drug: Afatinib
Afatinib will be administered orally once a day in a continuous regimen
Experimental: Phase 2 Combination with Cetuximab
Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC
 Drug: MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen

Drug: Cetuximab
Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental: Pilot Phase 1b Combination with Cetuximab in NSCLC
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC
 Drug: MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen

Drug: Cetuximab
Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental: Pilot Phase 1b Combination with Cetuximab in PDAC
Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)
 Drug: MRTX849
MRTX849 will be administered orally once or twice daily in a continuous regimen

Drug: Cetuximab
Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks


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 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 [ Time Frame: 20 months ]
    Blood plasma concentration

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


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

  2. Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents [ Time Frame: 12 months ]
    Number of participants with dose limiting toxicity

  3. Evaluate the pharmacokinetics of new MRTX849 oral formulations [ Time Frame: 6 months ]
    Blood plasma concentration

  4. Evaluate the pharmacokinetics of MRTX849 administered with food [ Time Frame: 6 months ]
    Blood plasma concentration


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
  • 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
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): NCT03785249


Contacts
Layout table for location contacts
Contact: Mirati Therapeutics Study Locator Services 1-844-893-5530 miratistudylocator@emergingmed.com

Locations
Show Show 98 study locations
Sponsors and Collaborators
Mirati Therapeutics Inc.
Investigators
Layout table for investigator information
Study Director: Hirak Der-Torossian Mirati Therapeutics
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Mirati Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03785249    
Other Study ID Numbers: 849-001
First Posted: December 24, 2018    Key Record Dates
Last Update Posted: January 9, 2023
Last Verified: January 2023
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
NSCLC
Colorectal Cancer
Colon Cancer
Metastatic Cancer
 Pancreatic Cancer
Adagrasib
STK11 mutation
KRAS G12C
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Pembrolizumab
Cetuximab
Afatinib
 Adagrasib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors