This study aims to observe the efficacy and safety of the combination of vebecotototo monoclonal antibody and putli monoclonal antibody in the treatment of EGFR-positive refractory biliary malignant tumors.

Inclusion criteria:

1. Age 18 - 70 years old, gender not restricted;

2. Patients with untreated primary advanced biliary system malignancies diagnosed by pathological histology or cytology;

3. Physical condition: ECOG PS score 0 - 1;

4. Pathological laboratory assessment: EGFR IHC ≥ 1+;

5. Have undergone at least one line of systemic drug treatment;

6. According to the RECIST 1.1 standard, at least one measurable target lesion that can be detected by CT or MRI;

7. Laboratory test indicators meet the following requirements:

   ① Bone marrow function: Hemoglobin (Hb) ≥ 90g/L; White blood cell count (WBC) ≥ lower limit of normal value; Absolute neutrophil count (ANC) ≥ 1.5×10^9/L; Platelet count ≥ 100×10^9/L;

   ② Renal function: Cr ≤ UNL (upper limit of normal) × 1.5, endogenous creatinine clearance rate (Ccr) ≥ 55 ml/min;

   ③ Liver function: Total bilirubin ≤ ULN × 1.5; ALT and AST ≤ ULN × 2.5; (if it is intrahepatic cholangiocarcinoma or there is liver metastasis, total bilirubin not higher than 3 times the upper limit of normal, transaminase not higher than 5 times the upper limit of normal);

   ④ Coagulation function: International normalized ratio of prothrombin time ≤ ULN × 1.5, and partial thromboplastin time within the normal range;

8. Pregnant women agree to use contraception during the study period and within 6 months after the study ends; The serum or urine pregnancy test is negative within 7 days before the study entry, and non-lactating patients; Male patients agree to use contraception during the study period and within 6 months after the study ends;

9. Within 4 weeks before entry, have not participated in other drug clinical trials;

10. The subject can understand the situation of this study and voluntarily sign the informed consent form.

11. No severe complications such as active gastrointestinal bleeding, perforation, jaundice, gastrointestinal obstruction, non-cancerous fever > 38℃;

12. Expected good compliance, able to follow the protocol requirements for efficacy and adverse reactions follow-up.

13. Expected survival period > 3 months.

Exclusion criteria:

(1) Previously diagnosed with other malignant tumors within 5 years (excluding carcinoma in situ, basal cell carcinoma, etc.); (2) Known central nervous system metastasis (except for those with stable disease after radiotherapy or surgery for 4 weeks and no symptoms) or evidence of cancer meningitis; (3) Have mental or neurological disorders and cannot cooperate; (4) Patients who have received drugs with a loading dose of MMAE ADC drugs previously; (5) Patients preparing for or having previously received organ or bone marrow transplantation; (6) Have any active autoimmune diseases or autoimmune disease history; (7) Received live vaccines within 30 days before the first administration (allowing the use of injectable seasonal influenza vaccine as it is a killed vaccine); (8) Have uncontrolled clinical symptoms or diseases of interstitial lung disease or active non-infectious pneumonia history or evidence; (9) Have interstitial lung disease or active non-infectious pneumonia history or evidence within 4 weeks before entry; (10) Have other diseases that are not suitable for entry, such as immunodeficiency, active pulmonary tuberculosis, hepatitis B (with HBV-DNA < 500IU/ml and normal liver function after treatment can be enrolled), hepatitis C virus positive, uncorrectable electrolyte disorders, uncontrollable pericardial effusion, pleural effusion and ascites, etc.; (11) Allergic to any drug in this protocol; (12) Within 14 days before entry, used immunosuppressive drugs or corticosteroids > 10mg/day prednisone at the efficacy dose; (13) Within 4 weeks before entry, received radiotherapy, chemotherapy, targeted therapy or immunotherapy; (14) Pregnant or lactating women; The researchers considered those who were not suitable for inclusion in the study.

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