City of Hope is ranked among the top five cancer hospitals in the nation according to U.S. News and World Report. The hospital works collaboratively with biopharmaceutical companies introducing cancer therapies to patients with an emphasis on people who have been diagnosed with colorectal cancer.
Researchers at the City of Hope reported the results of its Phase 3 trial called CodeBreak 300 using sotorasib, a KRAS G12C inhibitor, and showing an improved outcome for patients who were diagnosed with KRAS G12C metastatic colorectal cancer which no longer responds to chemotherapy.
The treatment was FDA approved in January 2025.
Patients were treated with two drugs:
- sotorasib, and
- the monoclonal antibody panitumumab
The study was reported in MedicalXpress and published in the journal Clinical Oncology.
Patients treated with the two-drug combination had a longer period of survival that was progression-free compared to patients receiving the current standard of care.
Dr. Marwan Fakih, senior author and City of Hope Gastrointestinal Cancer Co-director, suggested that the new treatment option should replace the current standard of care as it prolongs control of the cancer.
A Genetic Mutation
KRAS is a genetic mutation that activates the KRAS protein causing tumor growth and progression. KRAS mutations have been found in up to forty-five percent of cases of colorectal cancer.
These mutations are one of several KRAS mutations that exist in about 45% of colorectal cases.
About Sotorasib
Sotorasib is the first KRAS inhibitor that the FDA has approved for use in clinics.
The KRAS G12C inhibitor binds to the KRAS G12C protein and blocks its activation thereby inhibiting the growth of cancer cells.
About Panitumumab
Panitumumab is lab-produced and blocks epidermal growth factor receptors (EGFR) that are important for cell growth and division. EGFR is produced at a higher-than-normal level in colorectal cancer and several other cancers.
The study finds that sotorasib showed greater efficacy when combined with panitumumab. Patients (N160) participating in the trial’s three groups had been diagnosed with colorectal cancer which had progressed in spite of previous treatments.
Dr. Fakih explained that the increased dose of sotorasib matched the improved response rates as well as longer time to progression when compared with the control group.
The doctor added that over thirty percent of the group that was treated with sotorasib at an increased dose saw an objective response, defined as the tumor volume shrinking over 50%, compared to 1.9% shrinkage for the standard of care group.
Overall survival in the high dose sotorasib cohort was increased 30% when compared against the standard of care.
Common Adverse Reactions
About Adverse Events
Adverse reactions resulting from the trial were mostly diarrhea, nausea, musculoskeletal pain, fatigue, and hepatotoxicity (liver damage).
Dr. Fakih described the response rates as being “exciting” and that they provide a rationale for the combination of sotorasib, panitumumab and chemotherapy in the earlier lines of the disease.
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City of Hope Clinical Oncology Clinical Trials colorectal cancer Genetic Mutation
Last modified: April 30, 2025
