PD-L1 Antibody Combined With CTLA-4 Antibody for Patients With Advanced Intrahepatic Cholangiocarcinoma Who Progressed After Standard Treatment: a Single-arm, Phase II Clinical Study
Overview
- Phase
- Phase 2
- Intervention
- PD-L1 antibody combined with CTLA-4 antibody
- Conditions
- Cholangiocarcinoma, Intrahepatic
- Sponsor
- Shanghai Zhongshan Hospital
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- objective response rate (ORR)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
The study aims to evaluate the efficacy and safety of PD-L1 antibody combined with the CTLA-4 antibody in patients with advanced ICC who progressed after standard treatment.
Detailed Description
The prognosis of unresectable and metastatic intrahepatic biliary tract cancer (ICC) is extremely poor. The median overall survival of first-line gemcitabine and cisplatin for advanced biliary tumors (including ICC) is only 11.7 months. Currently, there is no standard second-line or third-line treatment for advanced ICC, and there is an urgent need to develop new treatment methods to improve patient survival. Chronic inflammation caused by viral infections and bile duct stones is the most common potential risk factor for ICC. The abnormal immune system plays a key role in the occurrence and development of ICC. The immune checkpoint molecules PD-L1 and CTLA-4 are overexpressed in ICC, and they are obviously heterogeneous, so immunotherapy has potential value. Immune checkpoint inhibitors against PD-1/PD-L1 show a good objective remission rate in advanced biliary tumors (including ICC). CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors show significant clinical enhancement Role, CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors have been clinically studied in a number of solid tumors. In this phase II clinical study, we will evaluate the efficacy and safety of PD-L1 monoclonal antibody combined with CTLA-4 monoclonal antibody in patients with advanced ICC who progressed after standard treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For unresectable or metastatic or postoperative recurrence, histologically confirmed advanced ICC, provide enough tissue samples for PD-L1, CTLA-4 immunohistochemistry, and exome sequencing
- •The standard systemic treatment of advanced ICC (gemcitabine or platinum or fluorouracil) failed due to disease progression or toxicity
- •There are measurable lesions defined by RECIST standard v1.1
- •For patients with a history of liver chemoembolization, radiofrequency ablation/intervention, or radiotherapy, there must be measurable lesions outside the chemoembolization or radiotherapy area or measurable progression lesions at the chemoembolization or radiotherapy site
- •ECOG physical strength status ≤ 1
- •Life expectancy\> 3 months
- •Adequate renal function: creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥ 60mL/min/1.73 m2
- •Sufficient liver function: bilirubin ≤ 1.5 × ULN and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN
- •Sufficient bone marrow reserve: absolute value of neutrophils (ANC)\> 1500/mcl, platelets (Plts)\> 75,000/mcl, hemoglobin (Hgb) ≥ 9.0g/dl
- •Prothrombin time/activated partial thromboplastin time (PT/PTT) \<1.5 × ULN
Exclusion Criteria
- •Past treatment with CTLA-4 mAb
- •Hilar cholangiocarcinoma or extrahepatic cholangiocarcinoma or periampullary carcinoma or gallbladder cancer
- •Major surgery or radiotherapy within 4 weeks before enrollment
- •Active, known, or suspected autoimmune diseases
- •Congestive heart failure or symptomatic coronary artery disease within 3 months before enrollment
- •Cerebrovascular accident occurred in the past 6 months
- •Clinically significant bleeding, bleeding event, or thromboembolic disease occurred within 6 months
- •History of bowel perforation
- •A history of (non-infectious) pneumonia requiring steroid treatment or current pneumonia
- •Known history of human immunodeficiency virus (HIV) infection
Arms & Interventions
PD-L1 antibody combined with CTLA-4 antibody
After 4 cycles of PD-L1 antibody combined with CTLA-4 antibody treatment, PD-L1 monotherapy was maintained until the disease progressed or intolerable toxicity and adverse reactions or the medication was used for two years.
Intervention: PD-L1 antibody combined with CTLA-4 antibody
Outcomes
Primary Outcomes
objective response rate (ORR)
Time Frame: 12 months
the objective response rate (ORR) of advanced ICC patients who progressed after standard treatment with PD-L1 antibody SHR-1316 combined with CTLA-4 antibody IBI310
Secondary Outcomes
- Safety: the potential side effects(12 months)
- overall survival(18 months)
- Progression free survival(12 months)