Overview

This trial is a registrational Phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 compared with the investigator's choice of protocol in patients with locally advanced or metastatic biliary tract cancer who have failed prior platinum-based chemotherapy.

Eligibility

Inclusion Criteria:

1. Voluntarily sign the informed consent form and agree to comply with the protocol requirements;
2. No gender restriction, aged ≥18 years and ≤75 years;
3. Expected survival time ≥3 months;
4. Patients with locally advanced or metastatic biliary tract cancer;
5. Agree to provide archived tumor tissue specimens from the primary or metastatic lesion within 3 years, or fresh tissue samples;
6. Must have at least one measurable lesion as defined by RECIST v1.1;
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
8. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
9. No severe cardiac dysfunction, with left ventricular ejection fraction (LVEF) ≥50%;
10. Organ function levels must meet the specified requirements;
11. Urine protein ≤2+ or ≤1000 mg/24h;
12. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the start of treatment, with serum pregnancy testing excluding pregnancy, and they must be non-lactating; all enrolled patients (regardless of male or female) must practice adequate barrier contraception throughout the entire treatment period and for 6 months after the end of treatment.

Exclusion Criteria:

1. Use of chemotherapy, targeted therapy, biological therapy, etc., within 4 weeks or 5 half-lives prior to randomization;
2. Patients with locally advanced or metastatic biliary tract cancer who are suitable for curative local therapy;
3. Prior use of ADC drugs using topoisomerase I inhibitors as the toxin, or prior treatment with ADC drugs targeting EGFR and/or HER3;
4. History of severe cardiovascular or cerebrovascular disease within 6 months prior to screening;
5. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to screening;
6. Prolonged QTc interval, complete left bundle branch block, third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
7. Diagnosis of active malignancy within 3 years prior to randomization;
8. Hypertension poorly controlled by two antihypertensive medications, history of hypertensive crisis or hypertensive encephalopathy;
9. Poorly controlled blood glucose levels;
10. History of non-infectious interstitial lung disease (ILD) treated with steroids, etc.;
11. Concurrent pulmonary disease resulting in clinically severe respiratory impairment;
12. Patients with active central nervous system metastases;
13. Severe infection occurring within 4 weeks prior to randomization;
14. Patients with large serous cavity effusions, symptomatic serous cavity effusions, or poorly controlled serous cavity effusions;
15. Imaging findings indicating tumor invasion or encasement of major blood vessels in the abdomen, thorax, neck, or pharynx;
16. Serious non-healing wounds, ulcers, or fractures within 4 weeks prior to signing the informed consent form;
17. Clinically significant bleeding or obvious bleeding tendencies in trial participants within 4 weeks prior to signing the informed consent form;
18. Patients with a history of allergy to recombinant humanized antibodies or to any excipient component of BL-B01D1;
19. Positive for human immunodeficiency virus antibodies, active tuberculosis, active hepatitis B virus infection, or hepatitis C virus infection;
20. History of severe neurological or psychiatric disorders;
21. Trial participants planning to receive or having received a live vaccine within 28 days prior to randomization;
22. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.