Vebotolimab Combined With Ptorlimab for EGFR-positive Refractory Advanced Biliary Tract Malignancies

Inclusion criteria

• Age 18 to 75 years, regardless of gender;
• Patients with locally advanced or metastatic biliary tract malignancies confirmed by histopathological or cytological examination;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• EGFR immunohistochemistry (IHC) score ≥1+ as assessed by pathology laboratory;
• Previously received at least one line of systemic therapy;
• At least one measurable target lesion assessable by CT or MRI according to RECIST 1.1 criteria;
• Laboratory parameters meeting the following requirements:

① Bone marrow function: hemoglobin (Hb) ≥90 g/L; white blood cell count (WBC) ≥lower limit of normal; absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count ≥75×10⁹/L;

② Renal function: creatinine (Cr) ≤ upper limit of normal (ULN) ×1.5; creatinine clearance (Ccr) ≥55 mL/min;

③ Liver function: total bilirubin ≤ULN ×1.5; ALT and AST ≤ULN ×2.5; (for intrahepatic cholangiocarcinoma or patients with liver metastases, total bilirubin must not exceed 3 times ULN, and transaminases must not exceed 5 times ULN);

④ Coagulation function: international normalized ratio (INR) ≤ULN ×1.5, and activated partial thromboplastin time (aPTT) within normal range;

• Female of childbearing potential agrees to use effective contraception during the study and for 6 months after study completion; negative serum or urine pregnancy test within 7 days prior to enrollment, and non-lactating; male participants agree to use effective contraception during the study and for 6 months after study completion;
• No participation in other clinical trials involving investigational drugs within 4 weeks prior to enrollment;
• The subject understands the study and voluntarily signs an informed consent form;
• No severe complications such as active gastrointestinal bleeding, perforation, jaundice, gastrointestinal obstruction, or fever >38°C unrelated to cancer;
• Expected good compliance, able to follow up for efficacy and adverse events as per protocol;
• Estimated survival time greater than 3 months.

Exclusion criteria

• History of another malignant tumor diagnosed within the past 5 years (except carcinoma in situ, basal cell carcinoma, etc.);
• Known central nervous system metastasis (except those with stable disease control and no symptoms after radiotherapy or surgery for at least 4 weeks), or evidence of carcinomatous meningitis;
• Presence of psychiatric or neurological disorders preventing cooperation;
• Prior exposure to ADC drugs carrying MMAE payload;
• Intention to undergo or history of organ or bone marrow transplantation;
• Active autoimmune disease or history of autoimmune disease;
• Administration of live vaccines within 30 days prior to first dose (use of injectable seasonal influenza vaccine is permitted, as it is an inactivated vaccine);
• Uncontrolled cardiac symptoms or disease;
• Active infection or fever (excluding documented tumor-related fever);
• History or evidence of interstitial lung disease or active non-infectious pneumonia;
• Other medical conditions making the patient unsuitable for enrollment, such as immunodeficiency, active tuberculosis, hepatitis B (eligible if HBV-DNA <1000 IU/mL after treatment and liver function is normal), positive hepatitis C virus test, uncorrectable electrolyte disturbances, uncontrollable pericardial effusion, pleural effusion, or ascites;
• Allergy to any drug in this regimen;
• Use of immunosuppressive drugs or corticosteroids exceeding 10 mg/day prednisone equivalent dose within 14 days prior to enrollment. (14) Patients who have received radiation therapy, chemotherapy, targeted therapy, or immunotherapy within 4 weeks prior to enrollment;

(15) Pregnant or breastfeeding women; (16) Patients deemed unsuitable for enrollment by the investigator.