An Open-Label, Multicohort, Phase II Study of Atezolizumab in Advanced Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 474
- 试验地点
- 48
- 主要终点
- Non-progression Rate (NPR) at 18 Weeks
研究概览
简要总结
The primary efficacy objective for this study is to evaluate non-progression rate (NPR) at 18 weeks in participants with advanced solid tumors treated with atezolizumab, defined as the percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1, or according to disease-specific criteria for prostate cancer and malignant pleural mesothelioma.
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
- •Histologically documented advanced solid tumors that meet protocol-defined cohort specifications, have progressive disease at study entry, and have received at least one line of prior systemic therapy or for which no alternative therapy to prolong survival exists
- •Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or in freshly cut and unstained slides (exceptional cases) with an associated pathology report for central testing
- •Measurable disease as defined by RECIST v1.1 or disease-specific criteria for prostate cancer and malignant pleural mesothelioma
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Negative serum pregnancy test result within 14 days prior to study drug among women of childbearing potential
- •Life expectancy > 3 months
排除标准
- •Malignancies other than disease under study within 5 years prior to Day 1 of Cycle 1 except those with a negligible risk of metastasis or death
- •Uncontrolled tumor-related pain
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures >/=1 time per month
- •History of asymptomatic or symptomatic central nervous system (CNS) metastasis
- •Leptomeningeal disease
- •Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated but without evidence that disease has been clinically stable for >/=2 weeks prior to Day 1 of Cycle 1
- •Pregnant and lactating women
- •Significant cardiovascular disease within 3 months prior to Day 1 of Cycle 1
- •Severe infection within 4 weeks prior to Day 1 of Cycle 1
- •Oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- •Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
- •History of autoimmune disease except treated/stable hypothyroidism, Type 1 diabetes mellitus, and protocol-specified dermatologic conditions
- •Active tuberculosis
- •Signs or symptoms of infection within 2 weeks prior to Day 1 of Cycle 1
- •Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, or anti-programmed cell death-1 (PD-1) or anti-PD-L1 therapeutic antibodies
- •Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to Day 1 of Cycle 1, or anticipated requirement for systemic immunosuppressive medications during the trial
研究组 & 干预措施
Atezolizumab
The dose of atezolizumab in this study will be 1200 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of each 3-week cycle until disease progression or unacceptable toxicity.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody (Drug)
结局指标
主要结局
Non-progression Rate (NPR) at 18 Weeks
时间窗: At Week 18
NPR was defined as the percentage of participants with complete response (CR), partial response (PR) or stable disease (SD) as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 or for malignant pleural mesothelioma according to Malignant Pleural Mesothelioma Response Evaluation Criteria. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions in the absence of CR. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: At least a 20% increase in the sum of diameters of all target and all new measurable lesions. For prostate cancer according to Prostate Response Evaluation Criteria. CR: PSA \<5 ng/ml measured twice at least 3 weeks apart or PSA response: PSA \< 50% of the PSA reference value occurring at any time after treatment was initiated.
次要结局
- Time to Progression (TTP)(Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first))
- Overall Survival (OS)(Baseline until death due to any cause (up to 4.5 years))
- Number of Participants With Adverse Events(Baseline up to 4.5 years)
- Treatment Duration of Atezolizumab(Baseline up to approximately 4.5 years)
- Mean Number of Doses of Atezolizumab(Baseline up to approximately 4.5 years)
- Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab(Baseline up to 4.5 years)
- NPR at 24 Weeks(At Week 24)
- Overall Response Rate (ORR)(Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first))
- Percentage of Participants by Best Overall Response (BOR)(Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first))
- Clinical Benefit Rate (CBR)(Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first))
- Duration of Objective Response (DOR)(Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first))
- Progression-Free Survival (PFS)(Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first))
- Serum Concentration of Atezolizumab(Predose and postdose on Day 1 of Cycle 1, predose on Day 1 of Cycles 2, 3, 4, 8 (cycle length = 21 days), and every 8 cycles until treatment discontinuation; at follow up (approximately 120 days after last dose) up to approximately 4.5 years)
- Percentage of Participants by Best Overall Response Based on Modified RECIST v1.1 (mBOR)(Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first))
- ORR Based on Modified RECIST v1.1(Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first))
- CBR Based on Modified RECIST v1.1(Baseline up to 4.5 years (assessed every 6 weeks for first 24 weeks and thereafter every 12 weeks up to loss of clinical benefit, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first))