Cancer of Biliary Duct
Conditions
Brief summary
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.
Interventions
DRUGVibecotecotamab combined with Putilimab for EGFR-positive refractory biliary malignant tumors
This study is a single-arm, prospective, phase II clinical trial, aiming to enroll patients with advanced biliary system tumors who have failed at least one line of standard treatment and are positive for EGFR. After the subjects sign the informed consent, those who are confirmed to meet the inclusion criteria undergo treatment with puzelimab, 200mg per dose, intravenous infusion on D1, once every 3 weeks; vibercept, 2.0mg/kg, intravenous infusion on D1, once every 3 weeks. The combination therapy will continue until disease progression or intolerable side effects occur.
Sponsors
West China Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 75 years, regardless of gender; 2. Patients with locally advanced or metastatic biliary tract malignancies confirmed by histopathological or cytological examination; 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; 4. EGFR immunohistochemistry (IHC) score ≥1+ as assessed by pathology laboratory; 5. Previously received at least one line of systemic therapy; 6. At least one measurable target lesion assessable by CT or MRI according to RECIST 1.1 criteria; 7. 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; 8. 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; 9. No participation in other clinical trials involving investigational drugs within 4 weeks prior to enrollment; 10. The subject understands the study and voluntarily signs an informed consent form; 11. No severe complications such as active gastrointestinal bleeding, perforation, jaundice, gastrointestinal obstruction, or fever \>38°C unrelated to cancer; 12. Expected good compliance, able to follow up for efficacy and adverse events as per protocol; 13. Estimated survival time greater than 3 months.
Exclusion criteria
1. History of another malignant tumor diagnosed within the past 5 years (except carcinoma in situ, basal cell carcinoma, etc.); 2. 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; 3. Presence of psychiatric or neurological disorders preventing cooperation; 4. Prior exposure to ADC drugs carrying MMAE payload; 5. Intention to undergo or history of organ or bone marrow transplantation; 6. Active autoimmune disease or history of autoimmune disease; 7. 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); 8. Uncontrolled cardiac symptoms or disease; 9. Active infection or fever (excluding documented tumor-related fever); 10. History or evidence of interstitial lung disease or active non-infectious pneumonia; 11. 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; 12. Allergy to any drug in this regimen; 13. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| overall response rate (ORR) | Up to 2 years | Description: The total number of participants in the intention-to-treat (ITT) population who achieve a complete response (CR) or partial response (PR) will be considered valid, and the statistical results were used to calculate the ORR based on imaging (CT/MRI) using the RECIST v1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | Up to 2 years | Progression-free survival (PFS): It refers to the period from the first day of using the study drug until the first radiological assessment of disease progression (PD) or death due to any cause. If the subject does not experience PD or death by the study's cut-off date, or has received other anti-tumor treatment, the last efficacy assessment result before the cut-off date or the start date of other anti-tumor treatment (whichever occurs first) will be used as the censored time. |
| Disease Control Rate (DCR) | Up to 2 years | The percentage of cases that achieved remission and stable lesion after treatment among all the evaluable cases. |
| Overall Survival (OS) | Up to 2 years | It refers to the period from the day the research drug was first used until death occurred for any reason. The end For the subjects who were still alive at the next follow-up, their OS was defined as data censored based on the last follow-up time. For the subjects who were lost to follow-up, their OS was defined as data censored based on the last confirmed survival time before the loss. The definition of censored OS is the time from enrollment to censoring. |
Countries
China
Contacts
CONTACTDan Cao
Outcome results
None listed