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Adagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2)

Sponsor
Mirati Therapeutics Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04330664
Collaborator
Novartis (Industry)
86
Enrollment
12
Locations
3
Arms
29.3
Anticipated Duration (Months)
7.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors that have a KRAS G12C mutation.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 in combination with TNO155 in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and TNO155 is a selective, orally bioavailable allosteric inhibitor of wild-type SHP2.

Study Design

Study Type:
Interventional
Actual Enrollment :
86 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Trial of MRTX849 in Combination With TNO155 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL 2
Actual Study Start Date :
Apr 22, 2020
Anticipated Primary Completion Date :
Sep 1, 2022
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1 Dose Exploration

Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849

Drug: MRTX849
KRAS G12C Inhibitor
Other Names:
  • adagrasib

    • Drug: TNO155
    SHP2 Inhibitor
    Experimental: Phase 1b Expansion

    Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens

    Drug: MRTX849
    KRAS G12C Inhibitor
    Other Names:
  • adagrasib

    • Drug: TNO155
    SHP2 Inhibitor
    Experimental: Phase 2

    Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination

    Drug: MRTX849
    KRAS G12C Inhibitor
    Other Names:
  • adagrasib

    • Drug: TNO155
    SHP2 Inhibitor

    Outcome Measures

    Primary Outcome Measures

    1. Characterize the safety of MRTX849 and TNO155 in patients having advanced solid tumor malignancies with KRAS G12C mutation. [20 months]

      Number of participants with treatment related adverse events

    2. Evaluate the pharmacokinetics of MRTX849 and TNO155 [20 months]

      Blood plasma concentration

    Secondary Outcome Measures

    1. Establish maximum tolerated dose [12 months]

      Number of participants with dose limiting toxicity

    2. Evaluate clinical activity of MRTX849 [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 2 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 UCLA Jonsson Comprehensive Cancer Center Los Angeles California United States 90095
    2 UC Irvine Health Orange California United States 92868
    3 Northwestern Chicago Illinois United States 60611
    4 Cancer Center of Kansas Wichita Kansas United States 67214
    5 Massachusetts General Hospital Boston Massachusetts United States 02114
    6 Dana Farber Boston Massachusetts United States 02215
    7 Henry Ford Detroit Michigan United States 48202
    8 Washington University School of Medicine Siteman Cancer Center Saint Louis Missouri United States 63110
    9 NYU Perlmutter Cancer Center New York New York United States 10016
    10 Memorial Sloan Kettering Cancer Center New York New York United States 10021
    11 NEXT Oncology San Antonio Texas United States 78229
    12 Froedtert Hospital & Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Mirati Therapeutics Inc.
    • Novartis

    Investigators

    • Study Director: Elise Walsh, MD, Mirati Therapeutics Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mirati Therapeutics Inc.
    ClinicalTrials.gov Identifier:
    NCT04330664
    Other Study ID Numbers:
    • 849-002
    First Posted:
    Apr 1, 2020
    Last Update Posted:
    Nov 22, 2021
    Last Verified:
    Nov 1, 2021
    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.
    KRAS G12C
    Non-small cell lung cancer
    Colorectal Cancer
    Colon Cancer
    Metastatic Cancer
    Pancreatic Cancer
    NSCLC
    SHP2
    Advanced Solid Tumors
    Additional relevant MeSH terms:
    Neoplasm Metastasis
    Neoplasms
    Adagrasib

    Study Results

    No Results Posted as of Nov 22, 2021