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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 : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Brief Summary:
This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 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

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 391 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 2020
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


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 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

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




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



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.


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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
  • Adequate organ function

Exclusion Criteria:

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

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
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Contact: Mirati Therapeutics Study Locator Services 1-844-893-5530 miratistudylocator@emergingmed.com

Locations
Show Show 56 study locations
Sponsors and Collaborators
Mirati Therapeutics Inc.
Investigators
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Study Director: Richard Chao Mirati Therapeutics
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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: October 8, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Pembrolizumab
Cetuximab
Afatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action