NCT04338269已完成3 期
A Phase III, Multicenter, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Atezolizumab Given in Combination With Cabozantinib Versus Cabozantinib Alone in Patients With Inoperable, Locally Advanced, or Metastatic Renal Cell Carcinoma Who Experienced Radiographic Tumor Progression During or After Immune Checkpoint Inhibitor Treatment
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 522
- 试验地点
- 125
- 主要终点
- Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1
研究概览
简要总结
This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of atezolizumab given in combination with cabozantinib versus cabozantinib alone in participants with inoperable, locally advanced, or metastatic renal cell carcinoma (RCC) who experienced radiographic tumor progression during or after Immune Checkpoint Inhibitor (ICI) treatment in the metastatic setting.
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
- •Histologically confirmed locally advanced or metastatic clear cell or non-clear cell (papillary, chromophobe, and unclassified only) RCC. RCC with sarcomatoid features is allowed. Patients with the chromophobe subtype of non-clear cell RCC must have sarcomatoid differentiation.
- •Radiographic disease progression to prior ICI therapy for RCC. Patients who experienced radiographic tumor progression during or within 6 months after the last dose of adjuvant ICI are also eligible. ICI is defined by anti-PD-L1 or anti-PD1 antibody including atezolizumab, avelumab, pembrolizumab, durvalumab, or nivolumab. Only patients for whom the immediate preceding line of therapy was an ICI are allowed.
- •Measurable disease per RECIST v1.1
- •Evaluable IMDC risk score
- •Archival tumor specimen, and pretreatment tumor tissue from fresh biopsy at screening, if clinically feasible. Both archival and fresh samples are preferred.
- •KPS score of >=70
- •Recovery to baseline or Grade </= 1 NCI CTCAE v5.0 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable in the opinion of the investigator. Grade 2 alopecia is allowed for study participation
- •Adequate hematologic and end-organ function
- •Negative HIV test at screening
- •Negative hepatitis B testing at screening
- •Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
- •For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm
排除标准
- •Treatment with anti-cancer therapy within 14 days prior to initiation of study treatment
- •Patients received cabozantinib at any time prior to screening
- •Patients who received more than one ICI treatment in the locally advanced or metastatic setting
- •Patients who received more than two prior lines of therapy in the locally advanced or metastatic setting
- •Patients who have received a mammalian target of rapamycin (mTOR) inhibitor in any setting
- •Symptomatic, untreated, or actively progressing CNS metastases
- •History of leptomeningeal disease
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Uncontrolled or symptomatic hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
- •History of malignancy other than renal carcinoma within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
- •Radiotherapy for RCC within 14 days prior to Day 1 of Cycle 1
- •Active tuberculosis
- •Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
- •Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after final dose of atezolizumab and 4 months after final dose of cabozantinib
- •Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact patient safety
- •Pharmacologically uncompensated, symptomatic hypothyroidism
- •Uncontrolled hypertension defined as sustained blood pressure >150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment (all countries except France); sustained BP > 140 mmHg systolic or > 90 mmHg diastolic despite optimal antihypertensive treatment (France only)
- •Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, unstable arrhythmia, or unstable angina) within 3 months prior to initiation of study treatment
- •Significant vascular disease (e.g., aortic aneurysm or arterial dissection requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of Cycle 1
- •History of congenital QT syndrome
- •History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
- •Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitor dabigatran, direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g. clopidogrel)
研究组 & 干预措施
Atezo+Cabo
Experimental
Participants will receive atezolizumab every 3 weeks on Day 1 of each 21-day cycle (1 cycle=21 days) plus oral tablets of cabozantinib every day.
干预措施: Atezolizumab (Drug)
Atezo+Cabo
Experimental
Participants will receive atezolizumab every 3 weeks on Day 1 of each 21-day cycle (1 cycle=21 days) plus oral tablets of cabozantinib every day.
干预措施: Cabozantinib (Drug)
Cabozantinib
Active Comparator
Participants will receive cabozantinib every day.
干预措施: Cabozantinib (Drug)
结局指标
主要结局
Progression Free Survival (PFS) as Assessed by an Independent Review Facility (IRF) (IRF-PFS) According to RECIST v1.1
时间窗: From randomization to the first occurrence of disease progression according to RECIST v1.1 (up to 2 years 5 months).
Progression Free Survival (PFS) is defined as the time from randomization to disease progression, as determined by the Independent Review Facility (IRF) per RECIST v1.1, or death from any cause, whichever occurs first. Data for patients who have not experienced disease progression or death were censored at the last tumor assessment date. Data for patients with no postbaseline tumor assessments were censored at the randomization date.
Overall Survival (OS)
时间窗: From randomization to death due to any cause (up to 2 years 5 months).
From randomization to death due to any cause. Data for patients who are not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Patients who do not have post-baseline information were censored at the date of randomization.
次要结局
- Independent Review Facility (IRF)-Assessed Overall Response Rate (ORR) (IRF-ORR) According to RECIST v1.1(From randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first) (up to 2 years 5 months).)
- Investigator-assessed Overall Response Rate (ORR) (INV-ORR) According to RECIST v1.1(From randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first) (up to 2 years 5 months).)
- Progression Free Survival (PFS) as Assessed by Investigators (INV-PFS), According to RECIST v1.1(From randomization to the first occurrence of disease progression according to RECIST v1.1 or death from any cause (whichever occurs first) (up to 2 years 5 months).)
- Investigator-assessed Duration of Response (DOR) (INV-DOR) According to RECIST v1.1(From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 2 years 5 months))
- Independent Review Facility (IRF)-Assessed Duration of Response (DOR) (IRF-DOR) According to RECIST v1.1(From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 2 years 5 months))
研究者
研究点 (125)
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