This is a phase Ib/II clinical study. All participants are patients with advanced colorectal cancer (CRC). The purpose of this study is to to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary anti-tumor efficacy of HDM2017 in combination with standard of care in patients with advanced CRC.

Inclusion Criteria:

1. Be able and willing to provide written informed consent.
2. Male or female participants with age ≥ 18 years.
3. Participants with histologically or cytologically confirmed unresectable locally advanced or metastatic colorectal adenocarcinoma.
4. Be able to provide archived tumor tissue during the screening period.
5. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
6. Life expectancy ≥3 months.
7. According to RECIST v1.1, participants must have at least one measurable lesion.
8. Has adequate organ function.
9. All subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 7 months after the last dose of study treatment.
10. Be willing and able to complete regular visits, treatment plans, laboratory tests, and other trial procedures.

Exclusion Criteria:

1. Participants who have previously received treatment with an anti-VEGFR tyrosine kinase inhibitor (TKI).
2. Participants who have previously received ADC therapy containing Top I inhibitors, or other drug therapy targeting the CDH17 target.
3. Participants with other malignant tumors within the past 5 years, other than the tumor being treated in this study, with the exception of locally cured tumors (such as basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, carcinoma in situ of the cervix or breast).
4. Related AEs from prior therapy (except for alopecia and ≤Grade 2 sensory neuropathy) have not recovered to ≤Grade 1 or baseline level.
5. Known weight loss of >10% within 2 months before the first dose of study drug or other indicators showing severe malnutrition.
6. History of severe esophagogastric varicose vein, severe ulcer, gastrointestinal perforation, abdominal fistula, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months before the first dose.
7. Participants with current imaging or clinical evidence of significant gastrointestinal obstruction.
8. Participants with clinically significant bleeding symptoms within 1 month before the first IMP dose.
9. Participants with known active CNS metastasis.
10. Participants with cardiovascular/cerebrovascular disorder, symptoms, or manifestations.
11. Participants with active syphilis, history of human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or active hepatitis C virus (HCV), except for asymptomatic chronic hepatitis B or C virus carriers.