Phase Ib Study to Evaluate the Pharmacokinetics, Safety and Efficacy of TQB2450 Injection(PD-L1 Antibody) Combined With Anlotinib in Subjects With Advanced Cholangiocarcinoma
试验速览
- 阶段
- 1 期
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Dose limiting toxicity (DLT)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.18 and 75 years; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months.
- •Histologically or cytologically confirmed inoperable or metastatic cholangiocarcinoma.
- •Providing tumor specimen obtained by biopsy or surgical sample within 2 years.
- •At least one measurable lesion.
- •Has failed with standard first-line chemotherapy or were not suitable for standard first-line chemotherapy.
- •6.The main organs function are normally.
- •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.
排除标准
- •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.
研究组 & 干预措施
Anlotinib + TQB2450
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).
干预措施: Anlotinib (Drug)
Anlotinib + TQB2450
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).
干预措施: TQB2450 (Drug)
结局指标
主要结局
Dose limiting toxicity (DLT)
时间窗: up to 21 days
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.
Maximum tolerated dose (MTD)
时间窗: up to 21 days
MTD defined as the highest dose level at which less than or equal to 2 of 6 subjects experience dose limiting toxicity (DLT)
Overall response rate (ORR)
时间窗: up to 24 months
Percentage of subjects achieving complete response (CR) and partial response (PR)
Recommended Phase II dose (RP2D)
时间窗: up to 24 months
The RP2D defined as the lower dose level to MTD based on the safety profile
次要结局
- Disease control rate（DCR）(up to 24 months)
- Progression-free survival (PFS)(up to 24 months)
- Overall survival (OS)(up to 24 months)
- Adverse Event(up to 24 months)