Adagrasib in Combination With BI 1701963 in Patients With Cancer (KRYSTAL 14)

Sponsor
Mirati Therapeutics Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04975256
Collaborator
Boehringer Ingelheim (Industry)
100
4
2
30.6
25
0.8

Study Details

Study Description

Brief Summary

This study will evaluate safety, tolerability, drug levels, molecular effects and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors that have a KRAS G12C mutation.

Detailed Description

This study will evaluate safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and BI 1701963 is a SOS1 pan-KRAS inhibitor.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/1b Trial of MRTX849 in Combination With BI 1701963 in Patients With Advanced Solid Tumors With KRAS G12C Mutation
Actual Study Start Date :
Aug 12, 2021
Anticipated Primary Completion Date :
Nov 30, 2023
Anticipated Study Completion Date :
Feb 28, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose escalation

Dose escalation of MRTX849 and BI 1701963 to determine maximum tolerated dose in combination

Drug: MRTX849
KRAS G12C inhibitor
Other Names:
  • KRAS G12C inhibitor
  • adagrasib
  • Drug: BI 1701963
    SOS1 Inhibitor
    Other Names:
  • SOS1 Inhibitor
  • Experimental: Dose expansion

    Expansion cohorts in NSCLC and CRC patients to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with BI 1701963

    Drug: MRTX849
    KRAS G12C inhibitor
    Other Names:
  • KRAS G12C inhibitor
  • adagrasib
  • Drug: BI 1701963
    SOS1 Inhibitor
    Other Names:
  • SOS1 Inhibitor
  • Outcome Measures

    Primary Outcome Measures

    1. Characterize the number of patients with treatment emergent adverse events of the combination regimen in patients with advanced solid tumor malignancies with KRAS G12C mutation [20 months]

      Number of participants with treatment related adverse events

    2. Evaluate Pharmacokinetics of the combination regimen [20 months]

      Blood plasma concentration

    3. Establish Maximum Tolerated Dose [12 months]

      Number of patients with dose limiting toxicity

    Secondary Outcome Measures

    1. Evaluate preliminary clinical activity of the combination regimen [20 months]

      Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 1b 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

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine Saint Louis Missouri United States 63110
    2 The Cleveland Clinic Foundation Cleveland Ohio United States 44195
    3 MD Anderson Cancer Center Houston Texas United States 77030
    4 Next Oncology San Antonio Texas United States 78229

    Sponsors and Collaborators

    • Mirati Therapeutics Inc.
    • Boehringer Ingelheim

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mirati Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT04975256
    Other Study ID Numbers:
    • 849-014
    First Posted:
    Jul 23, 2021
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Mirati Therapeutics Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 6, 2022