. 2023 Aug 7;23:729. doi: 10.1186/s12885-023-11188-4

Table 1.

Eligibility criteria

Key Inclusion Criteria	Key Exclusion Criteria
1. Histologically or cytologically confirmed locally advanced non-resectable or metastatic adenocarcinoma in the biliary tract, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer; 2. Aged 18 to 75 years, regardless of gender; 3. Expected life expectancy of ≥ 3 months; 4. ECOG PS of 0 or 1; 5. Documented disease progression after previous gemcitabine or fluorouracil-based systemic chemotherapy; not received any taxane therapy, including but not limited to paclitaxel, paclitaxel liposome, nab-paclitaxel, and docetaxel; 6. Measurable disease according to RECIST version 1.1. Assessment should be carried out within 28 days prior to study enrollment; 7. Adequate hematologic, hepatic, and renal functions (within 7 days before study entry): a. Hemoglobin ≥ 90 g/L b. Neutrophils ≥ 1500/mm³ c. Platelets ≥ 75,000/mm³ d. Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x ULN, or ≤ 5.0 x ULN in case of liver metastasis e. Bilirubin ≤ 1.5 x ULN f. Creatinine ≤ 1.5 x ULN g. Activated partial thromboplastin time, prothrombin time, and international normalized ratio ≤ 1.5 x ULN h. No prior blood transfusion, granulocyte colony-stimulating factor, or other medical support therapy; 8. In case of active hepatitis B or C, antiviral therapy starting at least 14 days before experimental drug administration and hepatitis B virus DNA ≤ 2500 copies/mL or ≤ 500IU/mL and hepatitis C virus RNA within the lower limit of detection; 9. Voluntarily participate and sign an informed consent.	1. Histologically confirmed squamous-cell carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, or sarcoma; 2. Malignancies of duodenal ampulla; 3. Severe hepatic or renal insufficiency; myocardial infarction within 3 months; 4. Patients with severe uncontrolled medical conditions or acute infections (infection-induced fever above 38 °C); 5. History of another malignancy with disease-free survival of less than 5 years, except for curative in situ cervical cancer, curative skin basal cell carcinoma, and curative gastrointestinal cancer by endoscopic mucoresection; 6. Current or past history of autoimmune diseases, including but not limited to interstitial lung disease, uveitis, enteritis, nephritis, hyperthyroidism, and hypothyroidism; 7. Active pulmonary tuberculosis within one year; 8. Suffering from interstitial lung disease or non-infectious pneumonia, or previous lung diseases may hinder the assessment or management of pulmonary toxicity associated with study drugs; 9. Severe infection requiring intravenous antibiotics, antifungal agents, or antiviral drugs; 10.Patients with a long history of chronic diarrhea or those with complete intestinal obstruction present; 11. Pregnant or breastfeeding female; unwillingness to use contraceptive measures in males and females; 12. Immunosuppressant or corticosteroid (systemic or local) used to suppress immune function within 2 weeks before inclusion; except for local or physiological doses of systemic glucocorticoids (e.g., no more than 10 mg/day of prednisone or other glucocorticoids of equivalent dose) by nasal spray, inhalation or other routes, or hormones used to prevent allergy; 13. Previous treatment with immunotherapy, such as anti-PD-1, anti-PD-L1, anti-PD-L2, or any other T-cell co-stimulation or checkpoint inhibitor therapy; 14. History of allergic disease or severe hypersensitivity to the experimental drugs; 15. Congenital or acquired immunodeficiency, such as HIV infection; 16. Other conditions deemed unsuitable for participation in this study by the investigators.

Key Inclusion Criteria

Key Exclusion Criteria

1. Histologically or cytologically confirmed locally advanced non-resectable or metastatic adenocarcinoma in the biliary tract, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer;

2. Aged 18 to 75 years, regardless of gender;

3. Expected life expectancy of ≥ 3 months;

4. ECOG PS of 0 or 1;

5. Documented disease progression after previous gemcitabine or fluorouracil-based systemic chemotherapy; not received any taxane therapy, including but not limited to paclitaxel, paclitaxel liposome, nab-paclitaxel, and docetaxel;

6. Measurable disease according to RECIST version 1.1. Assessment should be carried out within 28 days prior to study enrollment;

7. Adequate hematologic, hepatic, and renal functions (within 7 days before study entry):

a. Hemoglobin ≥ 90 g/L

b. Neutrophils ≥ 1500/mm³

c. Platelets ≥ 75,000/mm³

d. Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x ULN, or ≤ 5.0 x ULN in case of liver metastasis

e. Bilirubin ≤ 1.5 x ULN

f. Creatinine ≤ 1.5 x ULN

g. Activated partial thromboplastin time, prothrombin time, and international normalized ratio ≤ 1.5 x ULN

h. No prior blood transfusion, granulocyte colony-stimulating factor, or other medical support therapy;

8. In case of active hepatitis B or C, antiviral therapy starting at least 14 days before experimental drug administration and hepatitis B virus DNA ≤ 2500 copies/mL or ≤ 500IU/mL and hepatitis C virus RNA within the lower limit of detection;

9. Voluntarily participate and sign an informed consent.

1. Histologically confirmed squamous-cell carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, or sarcoma;

2. Malignancies of duodenal ampulla;

3. Severe hepatic or renal insufficiency; myocardial infarction within 3 months;

4. Patients with severe uncontrolled medical conditions or acute infections (infection-induced fever above 38 °C);

5. History of another malignancy with disease-free survival of less than 5 years, except for curative in situ cervical cancer, curative skin basal cell carcinoma, and curative gastrointestinal cancer by endoscopic mucoresection;

6. Current or past history of autoimmune diseases, including but not limited to interstitial lung disease, uveitis, enteritis, nephritis, hyperthyroidism, and hypothyroidism;

7. Active pulmonary tuberculosis within one year;

8. Suffering from interstitial lung disease or non-infectious pneumonia, or previous lung diseases may hinder the assessment or management of pulmonary toxicity associated with study drugs;

9. Severe infection requiring intravenous antibiotics, antifungal agents, or antiviral drugs;

10.Patients with a long history of chronic diarrhea or those with complete intestinal obstruction present;

11. Pregnant or breastfeeding female; unwillingness to use contraceptive measures in males and females;

12. Immunosuppressant or corticosteroid (systemic or local) used to suppress immune function within 2 weeks before inclusion; except for local or physiological doses of systemic glucocorticoids (e.g., no more than 10 mg/day of prednisone or other glucocorticoids of equivalent dose) by nasal spray, inhalation or other routes, or hormones used to prevent allergy;

13. Previous treatment with immunotherapy, such as anti-PD-1, anti-PD-L1, anti-PD-L2, or any other T-cell co-stimulation or checkpoint inhibitor therapy;

14. History of allergic disease or severe hypersensitivity to the experimental drugs;

15. Congenital or acquired immunodeficiency, such as HIV infection;

16. Other conditions deemed unsuitable for participation in this study by the investigators.

Abbreviations: ECOG, Eastern Cooperative Oncology Group; PS, performance status RECIST, Response Evaluation Criteria in Solid Tumors; ULN, upper limit of normal; PD-1, programmed cell death-1; PD-L1, programmed cell death-ligand 1; HIV, human immunodeficiency virus