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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 : April 11, 2024
Sponsor:
Information provided by (Responsible Party):
Mirati Therapeutics Inc.

Study Description
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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
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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 : December 26, 2018
Estimated Primary Completion Date : July 2025
Estimated Study Completion Date : January 2026

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Arms and Interventions
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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
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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
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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; 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
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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
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Sponsors and Collaborators
Mirati Therapeutics Inc.
Investigators
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Study Director: Hirak Der-Torossian Mirati Therapeutics
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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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: April 11, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Adagrasib
STK11 mutation
KRAS G12C
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Pembrolizumab
Cetuximab
Afatinib
Adagrasib
 Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Tyrosine Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors