A Randomized, Open-label , Multi-cohort, Multicenter, Phase II Study of Anlotinib Combined With AK105 Injection in Subjects With MSI-H or dMMR Advanced Solid Tumor
试验速览
- 阶段
- 2 期
- 入组人数
- 138
- 试验地点
- 9
- 主要终点
- Overall response rate (ORR) assessed by Independent Review Committee (IRC)
研究概览
简要总结
This study is designed to evaluate the efficacy and safety of Anlotinib combined with AK105 injection or AK105 monotherapy in subjects with MSI-H or dMMR advanced solid tumors. In this study, 138 subjects will be enrolled, and those who met the admission criteria will divide into cohort 1 (anlotinib combined with AK105) and cohort 2 (AK105 ). The first phase of this study is a randomized, open-label, parallel-controlled, multicenter design, in which 30 subjects are randomly enrolled in two cohorts. The second phase is to continue enrollment of cohort 1 or cohort 2 when which cohort has the better clinical benefit than the other one.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histopathologically confirmed MSI-H or dMMR advanced malignant solid tumors.
- •Has provided previously achieved tumor tissue samples or fresh samples.
- •18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy ≥ 3 months.
- •At least one measurable lesion.
- •The main organs function are normally. 6.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.
- •7.Understood and signed an informed consent form.
排除标准
- •1.Has used against PD-1, PD-L1 and other related immunotherapeutic drugs.
- •Has received chemotherapy, radiotherapy or other treatments within 4 weeks prior to the first dose.
- •Has brain metastases with symptoms or symptoms control for less than 2 months.
- •Has diagnosed and/or treated additional malignancy within 3 years prior to the first dose.
- •Has multiple factors affecting oral medication. 6.Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- •Has unrelieved spinal cord compression.
- •Imaging shows that tumors invade large blood vessels.
- •Has hemoptysis within 1 month prior to the first dose and maximum daily hemoptysis ≥2.5 mL.
- •Has adverse events caused by previous therapy except alopecia that did not recover to ≤grade
- •Has received surgery, or unhealed wounds within 4 weeks before the first dose.
- •Has artery/venous thrombosis prior to the first dose within 6 months.
- •Has drug abuse history that unable to abstain from or mental disorders.
- •Has any serious and / or uncontrolled disease.
- •Has received vaccination or attenuated vaccine within 4 weeks prior to the first dose.
- •Hypersensitivity to recombinant humanized anti-PD-1 monoclonal or its components.
- •Has active autoimmune diseases requiring systemic treatment occurred within 2 years before the first administration.
- •18.Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is required for the purpose of immunosuppression, and is still in use for 2 weeks after the first dose.
- •Has a history of active TB.
- •Has participated in other anticancer drug clinical trials within 4 weeks.
- •According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.
研究组 & 干预措施
Anlotinib+AK105 injection
AK105 200mg intravenously (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: AK105 (Drug)
Anlotinib+AK105 injection
AK105 200mg intravenously (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)
AK105 injection
AK105 200mg intravenously (IV) on day 1 of each 21-day cycle.
干预措施: AK105 (Drug)
结局指标
主要结局
Overall response rate (ORR) assessed by Independent Review Committee (IRC)
时间窗: up to 96 weeks
Percentage of subjects achieving complete response (CR) and partial response (PR) based on IRC.
次要结局
- Overall response rate (ORR) assessed by investigator(up to 96 weeks)
- Disease control rate（DCR）(up to 96 weeks)
- Duration of Response (DOR)(up to 96 weeks)
- Progression-free survival (PFS)(up to 96 weeks)
- Overall survival (OS)(up to 96 weeks)