Phase 3 Study of MRTX849 in Combination with Cetuximab VersusChemotherapy in Patients with Advanced Colorectal Cancer with KRAS G12C Mutation

A Randomized Phase 3 Study of MRTX849 in Combination with Cetuximab Versus Chemotherapy in Patients with Advanced Colorectal Cancer with KRAS G12C Mutation with Disease Progression On or After Standard First-Line Therapy

  • Clinical Trial Information

    Trial Contact: Britton, David ; Thomas, Andrea L; Donaldson, Karin M

  • IRB No: S21.012.01

    Protocol Abbrev: Mirati Krystal-10

    Principal Investigator: Omar R. Kayaleh, MD

    Phase: Drug: Phase III

    Age Group: Adult

    Secondary Protocol No: 849-010

    Treatment: test substances MRTX849 and cetuximab administered in combination. • reference substances FOLFIRI, comprised of irinotecan, folinic acid and 5-fluorouracil administered in combination, or mFOLFOX6, comprised of oxaliplatin, folinic acid and fluorouracil administered in combination.

    Therapies Involved: Chemotherapy ID: NCT04793958

  • Objective

    To compare the efficacy of MRTX849 in combination with cetuximab versus chemotherapy (FOLFIRI or mFOLFOX6) administered in the second-line treatment setting to patients with CRC with KRAS G12C mutation.

  • Key Eligibility

    1.Histologically confirmed diagnosis of colorectal carcinoma with KRAS G12C mutation in tumor tissue.

    2. Prior receipt of first-line treatment in the advanced disease setting with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan, and radiographically documented progression of disease on or after treatment.

    - Maintenance therapy given in the metastatic setting will not be considered a separate regimen.
    - Patients experiencing disease relapse during adjuvant treatment or within 6 months following completion of adjuvant therapy are eligible. Patients with relapse more than 6 months after completion of adjuvant therapy are not eligible.
    - Source documents for historical disease evaluations to allow Investigator certification of disease progression on or after first-line treatment must be available.
    3. Candidacy to receive treatment with cetuximab in accordance with the local product label, with the exception that patients must have documented KRAS G12C mutation
    and may or may not have demonstrated tumor positivity for EGFR-expression.
    4. Presence of evaluable or measurable disease per RECIST 1.1.
    5. Able to provide a sufficient amount of representative tumor specimen (primary or metastatic, archival or newly obtained) for central laboratory testing of KRAS G12C
    mutation status (minimum of 5 slides, preferably 15 slides).
    6. Age ≥18 years.
    7. Life expectancy of at least 3 months.
    8. Recovery from the adverse effects of prior therapy to baseline or Grade 1 (any grade alopecia and Grade ≤2 peripheral neuropathy are eligible). 849-010 v1.0 – Phase 3 in CRC with KRAS G12C Mutation Confidential
    MRTX849 with Cetuximab
    9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    10. Laboratory values within the screening period:
    a. Absolute neutrophil count 1,500/mm3 (1.5 × 109/L)
    b. Platelet count 100,000/mm3 (100 × 109/L)
    c. Hemoglobin ≥9.0 g/dL. Note: Transfusions will be allowed to achieve this
    provided the patient has not received more than 2 units of red blood cells in the
    prior 4 weeks
    d. Total bilirubin ≤1.5 × upper limit of normal (ULN); if associated with liver
    metastases, ≤3 × ULN.
    e. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × ULN; if associated with liver metastases, ≤5 × ULN.
    f. Creatinine clearance ≥60 mL/min.
    11. Able to take oral medications.
    12. Women of child-bearing potential (WOCBP) or men whose partner is a WOCBP agrees to use contraception while participating in this study, and for a period of 6 months following termination of study treatment.
    13. Completed informed consent process, including signing IRB/EC-approved informed
    consent form.
    14. Willing to comply with clinical trial instructions and requirements.