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8110 Gatehouse Road, Falls Church, VA 22042

A Randomized Phase III 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 (MIRATI KRYSTAL-10)

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General Information

Age Group

Adults

Status

Recruiting

Protocol Number

NCT04793958

Background Information

This is a study involving an investigational (experimental) drug called MRTX849, being developed by Mirati Therapeutics, Inc. This study will evaluate the effectiveness of the combination of MRTX849 with cetuximab in subjects with colorectal cancer who are experiencing progression on or after first-line chemotherapy.

MRTX849 has been administered to subjects with various kinds of cancer. The experience of those subjects was used to predict a safe starting dose of MRTX849 and to predict the kinds of side effects that might be seen. At the start of this study, it is unknown if the predictions made from the experience with MRTX849 will be correct.

Cetuximab (also known as ERBITUX®), is a cancer therapy that has been approved by the FDA for the treatment of people with colorectal cancer who do not have a KRAS mutation in their tumor. Cetuximab alone is not effective for people with colorectal cancer who have a KRAS mutation in their tumor.

This study will compare the effectiveness of MRTX849 in combination with cetuximab (investigational arm) versus standard of care second-line study treatment consisting of either FOLFIRI or mFOLFOX6 chemotherapy (comparator arm) in subjects with advanced colorectal cancer who have a specific change in tumor genes (KRAS G12C) and who are experiencing progression on or after first-line chemotherapy.

Other objectives of the study include evaluating the safety of MRTX849 in combination with cetuximab, assessing how quickly MRTX849 is absorbed into the blood stream and how fast it is removed, and evaluating health-related quality of life.

Offered At

Inova Schar Cancer Institute
8081 Innovation Park Drive
Fairfax, VA 22031
A department of Inova Fairfax Hospital

Eligibility Information

  • Histologically confirmed diagnosis of colorectal carcinoma with KRAS G12C mutation in tumor tissue
  • 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. Notes:
    • 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.
  • Age ≥ 18 years
  • Recovery from the adverse effects of prior therapy to baseline or Grade 1 (any grade alopecia and Grade ≤ 2 peripheral neuropathy are eligible)
  • Able to take oral medications
  • 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
  • Additional eligibility in protocol

Ineligibility Information

  • Prior treatment with both and oxaliplatin- and irinotecan-based regimen for CRC in the adjuvant and/or later treatment settings
  • Prior treatment with a therapy targeting KRAS G12C mutation (e.g., AMG 510)
  • Prior treatment with an anti-EGFR antibody (e.g., cetuximab or panitumumab)
  • Active brain metastases or carcinomatous meningitis. Patients are eligible if brain metastases are adequately treated and patients are neurologically stable for at least 2 weeks prior to randomization without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)
  • Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B or C infection. Note that the following are permitted:
    • Patients treated for hepatitis C (HCV) with no detectable viral load;
    • Patients treated for HIV with no detectable viral load for at least 1 month prior to randomization while on a stable regimen of agents that are not strong inhibitors of CYP3A4; and
    • Patients with hepatitis B (HBV) receiving prophylaxis against reactivation of hepatitis B (either [HBsAg-positive with normal ALT and HBV DNA < 2,000 IU/mL or <10,000 copies/mL] or [HBsAg-negative and anti-HBcpositive])
  • History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications
  • History of stroke or transient ischemic attack within 6 months prior to randomization
  • Ongoing need for treatment with concomitant medication known to cause prolonged QTc interval or known as strong inhibitor or inducer of CYP3A enzyme and that cannot be switched to alternative treatment prior to study entry
  • Known or suspected presence of another malignancy that could be mistaken for the malignancy under study during disease assessments
  • Pregnancy/breastfeeding
  • Additional ineligibility in protocol

Additional information can be found at: https://clinicaltrials.gov/ct2/show/ NCT04793958