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

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ClinicalTrials.gov Identifier: NCT03785249
Recruitment Status : Recruiting
First Posted : December 24, 2018
Last Update Posted : February 4, 2021
Sponsor:
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Tracking Information
First Submitted Date  ICMJE December 18, 2018
First Posted Date  ICMJE December 24, 2018
Last Update Posted Date February 4, 2021
Actual Study Start Date  ICMJE January 15, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • 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
  • Evaluate the pharmacokinetics of MRTX849 [ Time Frame: 20 months ]
    Blood plasma concentration
  • Evaluate clinical activity/efficacy of MRTX849 [ Time Frame: 20 months ]
    Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2018)
  • 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
  • Evaluate the pharmacokinetics of MRTX849 [ Time Frame: 20 months ]
    Blood plasma concentration
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • Establish maximum tolerated dose [ Time Frame: 12 months ]
    Number of participants with dose limiting toxicity
  • Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents [ Time Frame: 12 months ]
    Number of participants with dose limiting toxicity
  • Evaluate the pharmacokinetics of new MRTX849 oral formulations [ Time Frame: 6 months ]
    Blood plasma concentration
  • Evaluate the pharmacokinetics of MRTX849 administered with food [ Time Frame: 6 months ]
    Blood plasma concentration
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2018)
  • Establish maximum tolerated dose [ Time Frame: 12 months ]
    Number of participants with dose limiting toxicity
  • Evaluate clinical activity of MRTX849 [ Time Frame: 20 months ]
    Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1
Official Title  ICMJE A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Cancer
  • Metastatic Cancer
  • Malignant Neoplastic Disease
Intervention  ICMJE
  • 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
  • Drug: Cetuximab
    Cetuximab will be administered as an intravenous infusion once per week
  • Drug: Afatinib
    Afatinib will be administered orally once a day in a continuous regimen
Study Arms  ICMJE
  • Experimental: Phase 1 Dose Exploration
    Dose escalation of MRTX849 to determine maximum tolerated dose
    Intervention: Drug: MRTX849
  • 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
    Intervention: Drug: MRTX849
  • Experimental: Phase 2
    Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity of MRTX849
    Intervention: Drug: MRTX849
  • 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
    Interventions:
    • Drug: MRTX849
    • Drug: Pembrolizumab
  • 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
    Interventions:
    • Drug: MRTX849
    • Drug: Cetuximab
  • 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
    Interventions:
    • Drug: MRTX849
    • Drug: Afatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 29, 2020)
391
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2018)
200
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mirati Therapeutics Study Locator Services 1-844-893-5530 miratistudylocator@emergingmed.com
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03785249
Other Study ID Numbers  ICMJE 849-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Mirati Therapeutics Inc.
Study Sponsor  ICMJE Mirati Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Richard Chao Mirati Therapeutics
PRS Account Mirati Therapeutics Inc.
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP