Study of Becotatug Vedotin Added to Standard Treatment for Advanced Bile Duct Cancer With EGFR Mutations

A Randomized, Controlled, Open-Label, Multi-center Study of Becotatug Vedotin (EGFR-ADC) Combined With Chemo and Immunotherapy vs. Chemo and Immunotherapy as First-Line Treatment in Advanced/Metastatic EGFR-Mutated Biliary Tract Cancer

This study tests whether adding becotatug vedotin (EGFR-ADC) to standard chemotherapy plus immunotherapy improves outcomes compared to chemotherapy plus immunotherapy alone as first-line treatment for patients with advanced or metastatic biliary tract cancer whose tumors carry EGFR mutations. Participants will be randomly assigned to receive either the experimental combination (becotatug vedotin + pucotenlimab + gemcitabine + cisplatin) or the control combination (pucotenlimab + gemcitabine + cisplatin). The main goal is to see if the experimental group has a higher objective response rate (tumor shrinkage rate). This is a randomized, controlled, open-label, multicenter study led by Sir Run Run Shaw Hospital, Zhejiang University, with Dr. Chen Mingyu as the principal investigator.

Inclusion Criteria:

• Age ≥ 18 years old, both genders are eligible.
• Histologically confirmed unresectable or metastatic cholangiocarcinoma (including: gallbladder cancer, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma), histologically confirmed unresectable or metastatic cholangiocarcinoma (including: gallbladder cancer, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, after previous chemotherapy failure), and at least one assessable lesion.
• IHC test is positive for EGFR.
• ECOG PS score 0-1, normal major organ functions, no severe abnormalities in blood, heart, lungs, liver, kidneys, bone marrow and immune deficiency diseases.
• For female participants of childbearing age, a pregnancy test (serum/urine) result must be negative within 14 days before enrollment, and they must voluntarily use appropriate methods of contraception during the observation period and 8 weeks after the last administration of the study drug; for male participants, they should be surgically sterilized or agree to use appropriate methods of contraception during the observation period and 8 weeks after the last administration of the study drug.
• Expected good compliance, able to follow up on efficacy and adverse reactions as per the protocol requirements.
• Voluntary participation in this study and signing the informed consent form. If the participant is unable to read and sign the informed consent form due to lack of capacity, their guardian should act on their behalf in the informed process and sign the informed consent form. If the participant is unable to read the informed consent form (such as illiterate participants), a witness should witness the informed process and sign the informed consent form.

Exclusion Criteria:

• Within the 3 months prior to enrollment, the participant has not participated in any other clinical studies.
• Has any active autoimmune disease or history of autoimmune disease (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (after hormone replacement therapy can be included)); Has completely recovered from childhood asthma and does not require any intervention after adulthood or vitiligo can be included, but patients requiring bronchodilators for medical intervention are not included.
• Has congenital or acquired immune dysfunction, such as human immunodeficiency virus (HIV) infected individuals.
• Has uncontrolled clinical symptoms or diseases of the heart, such as NYHA II or above heart failure, unstable angina pectoris, myocardial infarction within 1 year, clinical significance of supraventricular or ventricular arrhythmias requiring clinical intervention.
• Had severe infection within 4 weeks before the first medication (such as requiring intravenous infusion of antibiotics, antifungal or antiviral drugs), or had unexplained fever > 38.5℃ during screening or before the first administration.
• Has a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Had vaccination with attenuated live vaccines within 4 weeks before the first administration or planned during the study period.
• Has had or is currently suffering from other systemic malignant tumors within the last 5 years (excluding cured skin basal cell carcinoma, cervical carcinoma in situ and ovarian cancer).
• Has known allergies to any study drug.
• Pregnant or lactating women, or subjects with reproductive capacity who are unwilling to take effective contraceptive measures.
• Vulnerable groups other than the elderly or illiterate, including those with mental illness, cognitive impairment, critically ill patients, etc.
• Other situations that the investigator deems unsuitable for inclusion in this study. Such as: the patient has central nervous system metastasis, has severe laboratory test abnormalities, is accompanied by family or social factors, which may affect the safety of the subject or the collection of data/samples.