A Study of BL-M07D1 Versus Physician's Choice of Chemotherapy in Patients With HER2-expressing Locally Advanced or Metastatic Biliary Tract Cancer After Platinum-containing Chemotherapy Failure

A Phase III Randomized Controlled Clinical Study of BL-M07D1 Versus Physician's Choice of Chemotherapy in Patients With HER2-expressing Locally Advanced or Metastatic Biliary Tract Cancer After Platinum-containing Chemotherapy Failure

This trial is a registrational Phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-M07D1 in patients with HER2-expressing locally advanced or metastatic biliary tract cancer after platinum-containing chemotherapy failure.

In this trial, the treatment group will receive BL-M07D1, and the control group will receive the physician's choice of chemotherapy.

Inclusion Criteria:

1. Voluntarily sign the informed consent form and comply with the protocol requirements;
2. Be ≥18 years and ≤75 years old on the day the trial participant signs the informed consent form;
3. Have an expected survival time of ≥3 months;
4. Have a histologically or cytologically confirmed pathological diagnosis of biliary tract cancer;
5. Have locally advanced or metastatic biliary tract cancer;
6. Have a known genetic mutation;
7. Be suitable to receive the control arm regimen;
8. Have at least one measurable lesion as defined by RECIST v1.1;
9. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
10. Have recovered from previous anti-tumor therapy to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
11. Have no severe cardiac dysfunction, with a left ventricular ejection fraction (LVEF) ≥50%;
12. Meet the required organ function levels;
13. For premenopausal women of childbearing potential, a serum pregnancy test must be performed within 7 days before starting treatment, and the result must be negative for pregnancy; they must be non-lactating. All enrolled trial participants should practice adequate barrier contraception throughout the entire treatment period and for 7 months after the end of treatment.

Exclusion Criteria:

1. Received surgical treatment, radical radiotherapy, chemotherapy, etc., within 4 weeks prior to the first dose;
2. Patients with locally advanced or metastatic biliary tract cancer who are suitable for receiving curative-intent local therapy;
3. Previously treated with ADC drugs using camptothecin derivatives as the toxin;
4. History of severe cardiovascular or cerebrovascular disease within 6 months prior to screening;
5. Concomitant pulmonary disease resulting in severely impaired lung function;
6. Prolonged QTc interval, complete left bundle branch block, etc.;
7. Diagnosed with active malignant tumors within 3 years prior to study randomization;
8. Hypertension inadequately controlled by two antihypertensive medications;
9. Patients with poorly controlled blood glucose levels;
10. History of interstitial lung disease (ILD) / interstitial pneumonia, etc.;
11. Patients with active central nervous system (CNS) metastases;
12. Patients with a history of allergy to recombinant humanized antibodies or any excipient of BL-M07D1;
13. History of autologous or allogeneic stem cell transplantation;
14. Positive for human immunodeficiency virus (HIV) antibodies, active Hepatitis B virus infection, or active Hepatitis C virus infection;
15. Occurrence of severe infection, etc., within 4 weeks prior to the first dose of the study drug;
16. Patients with a prior history of severe biliary tract infection/bleeding and biliary fistula;
17. Presence of large serous cavity effusions, or serous cavity effusions with symptoms, etc.;
18. Receiving long-term systemic corticosteroid therapy (e.g., >10 mg/day of prednisone or equivalent) prior to randomization;
19. History of severe neurological or psychiatric disorders;
20. Occurrence of serious and non-healing wounds, ulcers, or bone fractures within 4 weeks prior to signing informed consent;
21. Patients with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to signing informed consent;
22. Intestinal obstruction, Crohn's disease, ulcerative colitis, chronic diarrhea, etc.;
23. Received other unapproved clinical study drugs or treatments within 4 weeks prior to study randomization;
24. Patients who plan to receive or have received a live vaccine within 28 days prior to the first dose;
25. Imaging findings indicate that the tumor has invaded or encased major blood vessels in the abdomen, chest, neck, or pharynx;
26. Presence of other serious physical conditions, laboratory abnormalities, or poor compliance, etc., that may increase the risk of participating in the study, interfere with the study results, or make the patient unsuitable for participation in the study as judged by the investigator.