Inclusion Criteria:
1. Subject must be able to comprehend and willing to sign an informed consent form (ICF).
2. Subject must have a pathologically or cytologically confirmed carcinoma (except neuroendocrine) of the biliary tract (intra-hepatic, extra-hepatic (hilar, distal) or gallbladder) that is not eligible for curative resection, transplantation, or ablative therapies. Tumors of mixed cholangiocarcinoma/hepatocellular carcinoma histology are excluded.
3. Subject must be 18-75 years of age at the time of signature of the ICF.
4. Subject must have an ECOG performance status of 0-1. Estimated life expectancy no less than 3 months.
5. Subject may not have received prior systemic treatment (chemotherapy or targeted therapy) for advanced BTC. Prior peri-operative chemotherapy is permitted provided it was completed \> 6 months from enrollment.
6. Subject must have a lesion that can be accurately assessed at baseline by CT or magnetic resonance imaging (MRI) and is suitable for repeated assessment in accordance with RECIST v1.1.
7. Subject must have normal organ and marrow function as defined below within 14 days of study entry:
1. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelets ≥ 75 × 10\^9/L, or hemoglobin ≥ 9 g/dL.
2. International normalized ratio (INR) \< 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anticoagulation treatment with an agent such as warfarin will not be candidates for the trial. Patients on anticoagulation with low molecular weight or heparinoids are protocol candidates.
3. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) unless liver metastasis or BTC in which case ≤ 5 × ULN is permitted at the investigator's discretion. Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3 × ULN.
4. Creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (measured or calculated by Cockcroft and Gault equation).
5. Baseline left ventricular ejection fraction (LVEF) ≥ 60% measured by echocardiography or Multiple Gated Acquisition Scan (MUGA)
Exclusion Criteria:
* Patients with any of the following were excluded from the study:
1. Any investigational agents or study drugs from a previous clinical study within 4 weeks of the first dose of study treatment.
2. Malignancies other than BTC within 5 years prior to study enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent, or breast ductal carcinoma in situ treated surgically with curative intent).
3. Prior history of brain metastasis (unless previously treated, asymptomatic and stable for at least 3 months) or organ transplant.
4. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment.
5. Active bleeding during the last 4 weeks prior to screening or in the investigator's judgment, the existence of high bleeding tendency lesions such as active gastrointestinal ulcers or prominent esophageal or gastric varices.
6. Significant cardiovascular disease, including:
1. Heart disease classified as New York Heart Association class III or IV.
2. Ongoing uncontrolled hypertension.
3. History of congenital long QT syndrome.
4. Ongoing prolonged QT interval corrected for heart rate using Fridericia's method (QTcF) defined as ≥ 470 msec.
7. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation).
8. Subjects with atrial fibrillation, that is well controlled with treatment, can be enrolled. Active heart disease including symptomatic heart failure (NYHA class 3 or 4), unstable angina pectoris, uncontrolled cardiac arrhythmia or interstitial lung disease. Prolonged QTcF interval \>480 msec.
9. Ongoing active, uncontrolled infection (must be afebrile for \> 48 hours off antibiotics).
10. With the exception of alopecia, any unresolved toxicities from prior therapy ≥Common Terminology Criteria for Adverse Events (CTCAE) Grade 2.
11. Pregnancy or breastfeeding. (Women must not be pregnant or breastfeeding since study drugs may harm the fetus or child. All females of childbearing potential \[not surgically sterilized and between menarche and 1 year post menopause\] must have a negative screening pregnancy test.)
12. History of human immunodeficiency virus infection.
13. History of autoimmune disease.
14. Ascertained hypersensitivity to gemcitabine, cisplatin, camrelizumab or apatinib, or drugs with similar chemical structures, or its inactive components. If there is suspicion that the subject may have an allergy, the subject should be excluded.
15. Psychiatric illness, other significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements. Judgment by the investigators that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
