KRAS is a common genetic mutation in tumors, and CRC is one of the tumors with a high KRAS mutation rate. The anti-tumor activity of KRAS G12C inhibitors combined with anti-EGFR anti-bodies have been proven in patients with advanced colorectal cancer, and one of them was approved for patients who have previously received standard treatment. However, Chinese patients still do not have access to these drugs. This study is to determine the efficacy and safety of KRAS G12C inhibitor JAB-21822 in combination with the second-line standard chemotherapy and bevacizumab in advanced colorectal cancer failed to standard therapy in Chinese population.

The study is aimed for patients with histologically confirmed advanced metastatic colorectal cancer with KRAS G12C mutation, patients enrolled will treated with JAB-21822 combined with standard second-line chemotherapy and bevacizumab until disease progression or intolerable toxicity or patient-initiated withdrawal from the study. Enrolled patients will undergo imaging assessments at baseline and every 6 weeks during the treatment period, the anti-tumor efficacy will be evaluated by the investigator according to RECIST v1.1. Safety assessment included vital signs, haematology, blood biochemistry and urinalysis and will be monitored regularly during the study period during treatment. Any discomfort experienced by the patients after administration of the drug will also be recorded.

Inclusion Criteria:

• Histologically (or cytologically) confirmed, unresectable metastatic colorectal cancer.
• KRAS G12C mutation.
• At least one measurable disease per RECIST v1.1; assessed within 28 days before first dose.
• Subject have withdrawn from the first-line chemotherapy due to disease progression or unacceptable toxicity; if first-line chemotherapy and maintenance therapy were received, disease progression must within three months; first-line chemotherapy regimens do not limit the use of antiangiogenic agents.
• Adequate bone marrow, liver and renal function.
• ECOG performance status 0-1.
• Informed consent has been signed.

Exclusion Criteria:

• Patients have received KRAS G12C inhibitors.
• Patients have received a first-line treatment, which include fluoropyrimidine, oxaliplatin and irinotecan.
• Patients who are pregnant or breastfeeding.
• Life expectancy of less than 3 months.
• Patients who had major surgery or significant trauma within 4 weeks prior to the first blood sample collection during the screening period, or expected to require major surgery during the study period.
• Patients with active ulcers and gastrointestinal bleeding.
• Prior history of interstitial lung disease or non-infectious pneumonia; history of active tuberculosis.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Patients with clinically diagnosed autoimmune disease; HIV, HCV positive; HBV-DNA beyond the normal range of the laboratory; Acute CMV infection.
• Patients with active central nervous system metastases requiring treatment.
• Patients with other malignancies within five years.
• Assessed by the investigator, patients who are unable or unwilling to comply with the requirements of the study protocol.