AK112 and Chemotherapy in First-line Metastatic Colorectal Cancer

Inclusion Criteria:

1. Signed informed consent.

2. Age ≥ 18 years and ≤ 75 years.

3. ECOG status of 0 or 1.

4. Estimated survival ≥ 3 months.

5. Subjects with histologically or cytologically confirmed metastatic colorectaladenocarcinoma.

6. Subjects who are not candidates for radical surgical resection or local therapy andhave not received systemic anti-tumor therapy in the recurrent or metastaticsetting. Subjects who have received prior neoadjuvant or adjuvant therapy and whosefirst discovery of recurrence or metastases is ≥ 12 months after the last dose ofneoadjuvant or adjuvant therapy are allowed to enroll.

7. At least one measurable disease based on RECIST v1.1.

8. Adequate organ function per protocol-defined criteria.

9. Women of childbearing potential and men with female partners of childbearingpotential must agree to use effective contraception during treatment and for atleast 180 days following the last dose of study treatment.

Exclusion Criteria:

1. Previous (within 3 years) or concurrent other malignant tumors, excluding those thathave been cured.

2. Participating in other interventional study within 4 weeks prior to the first studydrug administration.

3. Palliative local treatment for non-target lesions within 2 weeks prior to the firstadministration; received non-specific immunomodulatory therapy within 2 weeks priorto the first administration.

4. Current presence of uncontrolled combined disease.

5. Active clinical infections.

6. History of severe bleeding tendency or coagulation dysfunction.

7. Subjects with known active tuberculosis (TB); suspected active TB should be excludedby clinical examination, known active syphilis infection.

8. Received a live vaccine within 30 days prior to the study, or plan to receive a livevaccine during the study.

9. Current presence of significant radiographic or clinical manifestations of GIobstruction.

10. Toxicities of prior anticancer therapy have not resolved to ≤ Grade 1 (NCI-CTCAEversion 5.0).

11. Pregnant or lactating women.

12. Any condition considered by the investigator to be inappropriate for enrollment.

13. Local or systemic disease caused by non-malignancy, or disease or symptom secondaryto tumor, that can lead to higher medical risk and/or uncertainty in survival.