A Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule as Second-line Treatment in Subjects With Advanced Biliary Cancer

A Randomized, Open-label, Parallel Controlled, Multi-center Phase III Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule Versus Chemotherapy as Second-line Treatment in Subjects With Advanced Biliary Cancer

This study is a randomized, parallel controlled, multicentre phase III clinical trial to evaluate the efficacy and safety of TQB2450 combined with anlotinib versus chemotherapy as second-line treatment in subjects with advanced biliary cancer.

Inclusion Criteria:

• 1. Histologically or cytologically confirmed biliary adenocarcinoma, including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC) and gallbladder cancer (GBC).

2.18 years and older,Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months;Weight ≥40 kg or BMI ≥18.5.

3. At least one measurable lesion (based on RECIST 1.1). 4. Previous first-line gemcitabine or fluorouracil-based combination chemotherapy failed.

5.Adequate laboratory indicators. 6. No pregnant or breastfeeding women, and a negative pregnancy test. 7. Understood and Signed an informed consent form.

Exclusion Criteria:

• 1. Tumor disease and medical history:

  1. Has central nervous system metastases (CNS) and/or cancerous meningitis or leptomeningeal carcinomatosis;
  2. Has other malignant tumors within 5 years;
  3. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear;
  4. Severe bone damage caused by tumor bone metastasis;
  5. Has uncontrolled and repeated drainage pleural effusion, pericardial effusion, and ascites;
  6. Partial or complete intestinal obstruction and complete biliary obstruction that cannot be relieved; 2. Previous anti-tumor therapy:
  1. Has received Anlotinib Hydrochloride Capsules, Bevacizumab Injection, and immune checkpoint inhibitors such as PD-1, PD-L1, and CTLA-4 in prior treatment;
  2. Have received anti-tumor therapy within 4 weeks before the first administration;
  3. Unalleviated toxicity ≥ grade 1 due to any previous anticancer therapy; 3.Comorbidities and medical history:

  1. Active hepatitis B or C;

  2. Kidney abnormalities;

  3. Abnormal thyroid function;

  4. Cardiovascular abnormalities;

  5. Gastrointestinal abnormalities;

  6. History of immunodeficiency;

  7. Has risk of bleeding;

  8. Uncontrollable active bacterial, fungal or viral infections;

  9. Lung diseases, such as interstitial pneumonia, obstructive lung disease, and history of symptomatic bronchospasm;

  10. Allergies to the ingredients of the study drug;

  11. Have a history of neurological or psychiatric disorders

  12. According to the researcher's point of view, other severe, acute or chronic medical or mental illnesses or laboratory abnormalities that may increase the risks associated with participating in the study, or may interfere with the interpretation of the study results;

  13. Have a history of pituitary or adrenal dysfunction

  14. Has received major surgical treatment, open biopsy, or obvious traumatic injury within 28 days before the first administration;

  15. Long-term unhealed wound or fracture;

  16. Has drug abuse history that unable to abstain from or mental disorders; 4. Has participated in other clinical trials within 30 days before the study. 5. Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first administration.

      6. Pregnant or breastfeeding women. 7. According to the judgement of the investigators, there are other factors that may lead to the termination of the study.