GFH375 Plus Cetuximab vs Investigator's Choice of Treatment in KRAS G12D-Mutant Refractory Metastatic Colorectal Cancer

Inclusion Criteria:

• Willing to participate in the study and provide written informed consent
• Age ≥18 years at the time of signing informed consent; no sex restriction
• Histologically or cytologically confirmed colorectal cancer (CRC)
• KRAS G12D mutation confirmed by the central laboratory
• Disease progression or intolerance during or after prior systemic anticancer therapy
• At least one measurable lesion
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-1
• Investigator-assessed life expectancy ≥12 weeks
• Adequate function of major organs
• In the investigator's judgment, the participant is able to communicate effectively, adhere to the scheduled follow-up visits, and comply with the protocol requirements

Exclusion Criteria:

• Other malignancy that has progressed or required treatment within 3 years prior to randomization
• Known presence of other actionable/targetable driver gene alterations
• Leptomeningeal metastases, spinal cord compression, or active/symptomatic brain metastases
• Pleural effusion, ascites, or pericardial effusion requiring repeated puncture/drainage (≥2 times/month) or causing significant symptoms within 28 days prior to randomization
• Clinically significant severe cardiovascular disease
• Stroke, transient ischemic attack (TIA), or other severe cerebrovascular disease within 6 months prior to randomization
• High-risk factors for bleeding or perforation
• Concurrent interstitial lung disease, radiation pneumonitis, or immune-mediated pneumonitis that is clinically significant and requires treatment
• Major acute or chronic infectious disease
• Other poorly controlled systemic disease
• Prior targeted therapy against KRAS or RAS
• History of organ transplantation or planned organ transplantation
• Receipt of a live attenuated vaccine within 28 days prior to randomization, or planned vaccination with a live attenuated vaccine during the trial drug treatment period
• Pregnant or lactating women
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for study participation