None listed
Conditions
Interventions
Drug : Phase 1b
Tislelizumab : 200mg, IV, every 3 weeks, D1
Nab-paclitaxel : 50~100 mg/m2, IV, every 3 weeks, D1 and D8 (administering up to 16 cycles)
Gemcitabine : 1000mg/m2, IV, every 3 weeks,
Sponsors
Bundang CHA General Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Subjects with histologically confirmed biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer (except for neuroendocrine tumor and sarcoma without the evidence of adenocarcinoma, Mixed Cholangiocarcinoma and HCC, AOV ) 2) Subjects aged 19 years or older at the time of signing informed consent 3) Treatment-naïve patients with unresectable or metastatic biliary tract cancer at diagnosis, or subjects with metastasis and recurrence at least 6 months after curative surgery or adjuvant chemotherapy 4) Subjects who are capable of providing signed informed consent to comply with requirements and limitations described in the ICF and this protocol and express obvious and voluntary agreement prior to the start of the study 5) Measurable lesions according to RECIST v. 1.1 6) ECOG PS 0-1 within 14 days prior to the first dose 7) Life expectancy of at least 3 months 8) Subjects with adequate hematological function and hepatic function without using blood transfusion or growth factors within 14 days prior to the administration of the first dose of study drug • Hemoglobin (Hb) =9.0 g/dL. • Absolute neutrophil count (ANC) =1,500/µl • Platelet count =100,000/µl • Serum creatinine =1.5 × upper limit of normal (ULN) or creatinine clearance (CrCl) estimated by Cockcroft-Gault equation =45 mL/min • AST and ALT =3.0 × ULN (however, AST and ALT =5.0 × ULN for confirmed hepatic metastasis) • Serum total bilirubin =1.5 × ULN • International normalized ratio (INR) =1.5 or prothrombin time =1.5 × ULN • Activated partial thromboplastin time (aPTT) = 1.5 × ULN. 9) Reproductive Status • Female participants must have documented proof that they are not of Childbearing potential. • Negative serum pregnancy test within 7 days prior to the administration of the first dose of study drug • Female participants must agree not to breast feed after the time of consent and for at least 6 months after the administration of the last dose of study drug. • Female subjects receiving cisplatin must agree to use effective contraception for up to 14 months after the last dose, and male subjects must agree to use effective contraception for up to 11 months after the last dose. • Women of child bearing potential and Non-sterilized fertile men should agree to use at least two highly effective contraceptive methods concomitantly during all the study and for at least 6 months after the administration of the last dose of study drug. 10) Subjects with a left ventricular ejection fraction (LVEF) of =50% as measured by echocardiography or MUGA scan and those without serious valvular disorders or arrhythmias 11) Subjects with Corrected QT interval =470msec at Screening. 12) Subjects who are willing to provide tissue samples from tumor lesions by endoscopic biopsy or excisional biopsy
Exclusion criteria
Exclusion criteria: 1) Subjects with a history of receiving systemic chemotherapy, biological therapy, immunotherapy, and hormone therapy or participating in another clinical study due to unresectable, locally advanced, or metastatic biliary tract cancer. However, the previous adjuvant chemotherapy or radiation therapy is acceptable if the disease showed recurrence at least 6 months after the last dose of adjuvant chemotherapy or radiation therapy. 2) History of another primary malignancy within the last 5 years except for completely resected basal cell carcinoma, stage 1 squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma or superficial bladder cancer. 3) As judged by the investigator, subjects with residual adverse events from the previous therapy that may affect safety evaluation of the study products or subjects who cannot completely rule out the possibility of surgery at the time of study participation 4) Current or previous severe hypersensitivity to other antibody products Subjects with the current or previous use of tislelizumab, anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, or other antibodies to regulate T cells, or subjects who have a history of hypersensitivity to those antibodies. Known allergy or hypersensitivity to cisplatin, gemcitabine, nab-paclitaxel, and tislelizumab 5) Patients with active autoimmune disease or subjects with a history of chronic or recurrent autoimmune disease (Subjects with hypothyroidism requiring hormone replacement only, vitiligo, and psoriasis not requiring treatment are eligible to participate in the study if the safety is secured as judged by the investigator.) 6) Subjects with a current or previous history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging or clinical findings. Patients with radiation pneumonitis can be enrolled if stability is confirmed without a concern about recurrence of radiation pneumonitis. 7) Active peptic ulcer (a history of inflammation includes, but not limited to, diverticulitis or colitis) 8) Known central nervous system (CNS) metastasis 9) Pericardial fluid, pleural effusion or ascites requiring treatment 10) Uncontrolled tumor-related pain 11) Subjects who have experienced transient ischemic attack or cerebrovascular accident within 180 days prior to enrollment. 12) Subjects with a history of uncontrolled or severe cardiovascular diseases meeting any one of the following criteria: • Myocardial infarction within 180 days of enrollment • Uncontrolled angina within 180 days of enrollment • Congestive heart failure New York Heart Association (NYHA) Class III or IV • Uncontrolled hypertension even with appropriate treatment (e.g., persistent systolic blood pressure =150 mmHg or diastolic blood pressure =90 mmHg for 24 h or longer) • Arrhythmias requiring treatment • Subjects with significant vascular diseases including current thrombosis in peripheral artery and aortic aneurysm, requiring surgical restoration 13) Patients with uncontrolled diabetes mellitus 14) Systemic infections requiring treatment within 14 days prior to the first dose of study drug (however, the use of prophylactic antibiotics is an exception.) 15) Subjects who received systemic corticoids (except for temporary use for tests, prophylactic purpose, or similar purposes) or immunosuppressants (equivalent to >10 mg/day of prednisolone) within 28 days prior to the first dose of study drug 16) Subjects who have receive
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1b: determine the maximum tolerated dose and recommended Phase 2 dose of Nab-Paclitaxel;Phase 2: Objective response rate (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS);Progression-Free Survival (PFS);Disease Control Rate (DCR);Duration of Response (DOR);Quality of Life (QoL) assessed by EORTC QLQ-C30 and QLQ-BIL21;Safety and tolerability | — |
Countries
Korea, Republic of
Contacts
Public ContactMi Ri Jeong
Bundang CHA General Hospital
Outcome results
None listed