Study of TQB2450 Combined With Anlotinib in Subjects With Advanced Cholangiocarcinoma

Study Overview
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Brief Summary
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TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.

Official Title
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Phase Ib Study to Evaluate the Pharmacokinetics, Safety and Efficacy of TQB2450 Injection(PD-L1 Antibody) Combined With Anlotinib in Subjects With Advanced Cholangiocarcinoma

Conditions
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Advanced Cholangiocarcinoma

Intervention / Treatment
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* Drug: Anlotinib
* Drug: TQB2450


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.18 and 75 years; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months. 2. Histologically or cytologically confirmed inoperable or metastatic cholangiocarcinoma. 3. Providing tumor specimen obtained by biopsy or surgical sample within 2 years. 4. At least one measurable lesion. 5. Has failed with standard first-line chemotherapy or were not suitable for standard first-line chemotherapy. 6.The main organs function are normally. 7. Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ；No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization. 8.Understood and signed an informed consent form. Exclusion Criteria: Prior therapy with VEGFR-target TKI included anlotinib or an anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2, anti-tumor necrosis factor CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody ,or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Abm or its components. Has diagnosed and/or treated additional malignancy within 5 years prior to randomization. Exceptions include cured basal cell carcinoma of skin and carcinoma in situ of cervix. Has any active autoimmune disease or a history of autoimmune disease. Has immunosuppressive therapy with systemic or absorbable topical hormone therapy and replacement therapy for hypothyroidism with normal thyroid function within 2 weeks before the first dose. Has multiple factors affecting oral medication. Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Has any signs of bleeding or a history of physical illness. Has uncontrollable symptoms of brain metastasis, spinal cord compression, cancerous meningitis during screening within 8 weeks before first dose. Has received chemotherapy, surgery, radiotherapy, the last treatment from the first dose less than 4 weeks, or oral targeted drugs for less than 5 half-lives, or oral fluorouracil pyridine drugs for less than 14 days, mitomycin C and nitrosourea for less than 6 weeks. Has any serious and / or uncontrolled disease. Has vaccinated with vaccines or attenuated vaccines, or received granulocyte colony stimulating factor(G -CSF)，or Granulocyte macrophage colony stimulating factor (GM-CSF) within 4 weeks prior to first dose. According to the judgement of the researchers, there are other factors that may lead to the termination of the study. For example, other serious diseases including mental disorders need to be treated together, serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of the subjects, or the collection of data and samples.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib + TQB2450<br>TQB2450 1200 mg IV on Day 1 of each 21-day cycle plus Anlotinib capsules given orally in fasting conditions , once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). | Drug: Anlotinib<br>* a multi-target receptor tyrosine kinase inhibitor<br>Drug: TQB2450<br>* TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) | DLT defined as any of the following events occurring during the study related to drugs : (1) ≥grade 3 non-hematologic toxicity; (2) Grade 4 neutropenia, thrombocytopenia, and hemoglobin reduction confirmed by at least 2 tests within 2 days; Grade 3 thrombocytopenia with bleeding tendency confirmed by at least 2 tests within 2 days; (3) Grade 3 neutropenia with fever confirmed at least 2 times within 2 days. | up to 21 days | 
| Maximum tolerated dose (MTD) | MTD defined as the highest dose level at which less than or equal to 2 of 6 subjects experience dose limiting toxicity (DLT) | up to 21 days | 
| Recommended Phase II dose (RP2D) | The RP2D defined as the lower dose level to MTD based on the safety profile | up to 24 months | 
| Overall response rate (ORR) | Percentage of subjects achieving complete response (CR) and partial response (PR) | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate（DCR） | Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD) | up to 24 months | 
| Progression-free survival (PFS) | PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause | up to 24 months | 
| Overall survival (OS) | OS defined as the time from randomization to death from any cause. Subjects who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive | up to 24 months | 
| Adverse Event | Number of participants with adverse events | up to 24 months |