Tislelizumab（Anti PD-1), Lenvatinib and GEMOX Transformation in the Treatment of Potentially Resectable, Locally Advanced Biliary Tract Cancer

NCT05156788 | Unknown Phase 2

• 1 other identifier: ZSAB-TransGOLP
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of this study is to assess the R0 resection rate of tislelizumab combined with Lenvatinib and Gemox chemotherapy in the conversion therapy of potentially resectable locally advanced BTC.

Conditions

Biliary Tract Cancer; PD-1 Antibody; Gemox; Lenvatinib

Outcome Measures

Primary Outcomes (1)

• R0 resection rate

  the ratio of the number of R0 resection cases to the total number of enrolled cases

  24 months

Secondary Outcomes (7)

• ORR

  24 months

• DCR

  24 months

• PFS

  24 months

• OS

  24 months

• CPR

  24 months

Study Arms (1)

PD-1 antibody +Lenvatinib+Gemox

EXPERIMENTAL

Tilelizumab 200mg, d1 Q3W Lenvatinib 8mg, po, qd, Gemox chemotherapy Gemcitabine 1000mg/m2, d1, 8, Q3W, + oxaliplatin 85mg/m2 d1, Q3W

Drug: PD-1+Lenvatinib+GEMOX

Interventions

PD-1+Lenvatinib+GEMOX DRUG

Tilelizumab 200mg, add 0.9% NS 100mL, d1 Q3W, Lenvatinib 8mg, po, qd Gemox chemotherapy: Gemcitabine 1000mg/m2 with 0.9% NS 100mL, 30 minutes, d1, 8, Q3W, + oxaliplatin 85mg/m2 with 5%GS 500mL, 2 hours, d1, Q3W

PD-1 antibody +Lenvatinib+Gemox

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Male or female aged 18-70 2. The patient must sign an informed consent form before joining the group, understand and be willing to sign a written informed consent form 3. Potentially resectable locally advanced BTC (including ICC, PBDT and GBC) confirmed by histology or cytology, agree to provide previously stored tumor tissue specimens or fresh biopsy tumor lesions for biomarker detection 4. Local progress, failure to achieve R0 resection, and no distant metastasis, with potential resection 5. At least one measurable lesion (RECIST 1.1) 6. Have never received systemic treatment for biliary tumors in the past 7. Eastern Cooperative Oncology Group (ECOG) performance status score ECOG PS 0-1 8. Liver function classification is Child-Pugh A 9. The bone marrow, liver and kidneys are fully functional and reach the following clinical laboratory evaluation standards within 7 days before treatment:
• Blood indicators:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet ≥ 90 × 109/L, hemoglobin ≥ 90 g/L.
• Liver function indicators:
• AST and ALT are both ≤3×ULN (upper limit of normal value); total bilirubin ≤1.5×ULN
• Kidney function indicators:
• Serum creatinine≤1.5×ULN
• Coagulation index:
• International normalized ratio (INR) ≤ 1.2 or prothrombin time (PT) ≤ 1.2×ULN
• Obstructive jaundice, after PTCD or ERCP treatment, if the liver function indicators meet the requirements for entry, it can be considered for entry:
• \. If the subject has HBV or HCV infection, the following conditions must be met:
• For inactive/asymptomatic carriers of HBV, chronic, or active HBV:
• HBV deoxyribonucleic acid (DNA) \<2000 copies/mL during the screening period. Remarks: Patients with HBV DNA\>2000 copies/mL should be treated according to treatment guidelines. Patients who received antiviral drug treatment at the time of screening should have HBV-DNA \<2000 copies/mL and continue treatment during the study period.
• For subjects infected with HCV:
• If the infection is confirmed based on the detectable HCV ribonucleic acid RNA, such subjects cannot be included in the group.

You may not qualify if:

• \. Diagnosed as mixed type of periampullary carcinoma, hepatocellular carcinoma and cholangiocarcinoma 2. Have received systemic treatment for biliary tumors in the past 3. Have previously received gemcitabine-based chemotherapy or TKI therapy or any tumor immunotherapy (for example, PD-1/L1 inhibitors, CTLA-4 inhibitors, etc.) 4. Have a history of severe hypersensitivity to other monoclonal antibodies 5. Allergy to tislelizumab or any of its excipients; allergy to oxaliplatin and any of its excipients; allergy to gemcitabine and any of its excipients; allergy to lenvatinib and any of its excipients 6. The presence of pericardial effusion, uncontrollable pleural effusion or clinically obvious ascites within 7 days before treatment is defined as meeting the following criteria: (a) Ascites can be detected by physical examination during screening, or (b) during screening, Ascites requires puncture fluid.
• \. There is no clinical evidence of portal hypertension with esophageal or gastric varices within 6 months before starting treatment.
• \. Any bleeding or thrombotic disease or any anticoagulant (such as warfarin or similar drugs) that needs to monitor the international standardized ratio during treatment within 6 months before the start of treatment 9. Has suffered from any malignant tumors, except for the BTC studied in this clinical trial and locally recurring cancers that have been cured (such as resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast cancer) Carcinoma in situ, occult carcinoma of the thyroid).
• \. Any known central nervous system metastasis and/or leptomeningeal disease have been present before treatment.
• \. A history of any active immunodeficiency or autoimmune disease and/or any immunodeficiency or autoimmune disease that may recur at the time of screening
• Note: Subjects with the following diseases can be selected:
• Type I diabetes Hypothyroidism (if only hormone replacement therapy can be used to control) Controlled celiac disease Skin diseases that do not require systemic treatment (eg vitiligo, psoriasis, hair loss) Any other disease that will not recur without external triggers 12. Any disease requiring systemic treatment with corticosteroids (dose higher than 10mg/day of prednisone or equivalent doses of similar drugs) or other immunosuppressive agents in the 14 days before treatment.
• Remarks: Subjects who have currently or previously used any of the following steroid regimens can be selected:
• In the absence of active autoimmune diseases, adrenaline replacement steroids are allowed (prednisone ≤10mg/day or equivalent dose of similar drugs) Local, ophthalmic, intra-articular, intranasal and inhaled corticosteroids with minimal systemic absorption Prophylactic short-term use (≤7 days) corticosteroids (for example, allergy to contrast agents) or for the treatment of non-autoimmune conditions (for example, delayed hypersensitivity reactions caused by contact allergens) 13. There is a history of interstitial lung disease or non-infectious pneumonia.
• \. Any serious chronic infection or active infection (excluding viral hepatitis) that requires systemic antibacterial, antifungal or antiviral therapy (such as tuberculosis) before starting treatment.
• \. The electrocardiogram during screening showed that the QT interval (QTc) corrected according to the heart rate (corrected according to the Fridericia method) exceeded 450 msec.
• Note: If any patient finds that the QTc interval exceeds 450 msec during the first ECG examination, the ECG will be repeated to confirm the result.
• \. Any of the following cardiovascular risk factors: Cardiogenic chest pain in the 28 days before treatment, defined as moderate pain that restricts daily activities (ADL) Symptomatic pulmonary embolism occurred within 28 days before treatment A history of acute myocardial infarction occurred within 6 months before treatment.
• Any history of heart failure reaching New York Heart Association grade III or IV within 6 months of treatment Ventricular arrhythmia of grade ≥2 occurred within 6 months before treatment Cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within 6 months before treatment.
• \. Have received organ transplantation or hematopoietic stem cell transplantation (HSCT) or any major surgery within 28 days before treatment.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (2)

Zhongshan hospital

Shanghai, 200032, China

Location

Shenzhen University General Hospital

Shenzhen, China

Location

Related Publications (1)

• Shi G, Huang X, Li X, Liang F, Gao Q, Zhang D, Lu J, Ji Y, Hu Z, Chen Y, Qiu S, Yi Y, Zhu X, Sun H, Shi Y, Peng M, Wang X, Huang C, Ding Z, He Y, Shen Y, Xu Y, Xiao Y, Hu J, Zhou J, Fan J. Conversion therapy of tislelizumab plus lenvatinib and GEMOX in unresectable locally advanced biliary tract cancer (ZSAB-TransGOLP): a multicentre, prospective, phase 2 study. Lancet Oncol. 2025 Oct;26(10):1334-1345. doi: 10.1016/S1470-2045(25)00376-6. Epub 2025 Aug 29.

  PMID: 40889502 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Jia Fan

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2021
• First Posted: December 14, 2021
• Study Start: December 12, 2021
• Primary Completion: July 3, 2023
• Study Completion: October 1, 2025
• Last Updated: August 15, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)