A Phase III, Open-Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 915
- 试验地点
- 154
- 主要终点
- Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population
研究概览
简要总结
This multi-center, randomized, open-label study will evaluate the efficacy and safety of atezolizumab plus bevacizumab versus sunitinib in participants with inoperable, locally advanced, or metastatic RCC who have not received prior systemic active or experimental therapy, either in the adjuvant or 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
- •Definitive diagnosis of unresectable locally advanced or metastatic RCC with clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior treatment in the metastatic setting
- •Evaluable Memorial Sloan Kettering Cancer Center risk score
- •Measurable disease, as defined by RECIST v1.1
- •Karnofsky performance status greater than or equal to 70%
- •Adequate hematologic and end-organ function prior to randomization
排除标准
- •Disease-Specific Exclusions:
- •Radiotherapy for RCC within 14 days prior to treatment
- •Active central nervous system disease
- •Uncontrolled pleural effusion, pericardial effusion, or ascites
- •Uncontrolled hypercalcemia
- •Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death
- •General Medical Exclusions:
- •Life expectancy less than 12 weeks
- •Participation in another experimental drug study within 4 weeks prior to treatment
- •Pregnant or lactating women
- •Known hypersensitivity to any component of atezolizumab or other study medication
- •History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
- •Positive human immunodeficiency virus test
- •Active or chronic hepatitis B or C
- •Severe infections within 4 weeks prior to treatment
- •Exposure to oral or IV antibiotics within 2 weeks prior to treatment
- •Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)
- •Significant cardiovascular disease
- •Prior allogeneic stem cell or solid organ transplantation
- •Exclusion Criteria Related to Medications:
- •Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- •Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or immunosuppressive agents within 2 weeks prior to treatment
- •Bevacizumab- and Sunitinib-Specific Exclusions:
- •History of hypertensive crisis or hypertensive encephalopathy
- •Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds
研究组 & 干预措施
Atezolizumab + Bevacizumab
Participants will receive both atezolizumab and bevacizumab until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
干预措施: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug)
Atezolizumab + Bevacizumab
Participants will receive both atezolizumab and bevacizumab until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
干预措施: Bevacizumab (Drug)
Sunitinib
Participants will receive sunitinib until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.
干预措施: Sunitinib (Drug)
结局指标
主要结局
Percentage of Participants With Disease Progression as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death From Any Cause in Programmed Death-Ligand 1 (PD-L1)-Selected Population
时间窗: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
Tumor response was assessed by the investigator according to RECIST v1.1. Disease Progression (PD) was defined as greater than or equal to (\>/=) 20 percent (%) relative increase in the sum of diameters (SoD) of all target lesions (TLs), taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 millimeters (mm); \>/=1 new lesion(s); and/or unequivocal progression of existing non-TLs.
Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 in PD-L1-Selected Population
时间窗: Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months)
PFS was defined as the time from randomization to PD, as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurred first. PD: \>/=20% relative increase in the SoD of all TLs, taking as reference the smallest SoD on study, including baseline, and an absolute increase of \>/=5 mm; \>/=1 new lesion(s); and/or unequivocal progression of non-TLs. Participants without PFS event were censored at the last tumor assessment date. Participants with no post-baseline tumor assessments were censored at the randomization date + 1 day. Participants with a PFS event who missed \>/=2 scheduled assessments immediately prior to the PFS event were censored at the last tumor assessment prior to the missed visits. Median PFS was estimated by Kaplan-Meier method and 95% confidence interval (CI) was assessed using the method of Brookmeyer and Crowley.
Percentage of Participants Who Died of Any Cause in ITT Population
时间窗: Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)
Percentage of participants who died of any cause was reported.
Overall Survival (OS) in ITT Population
时间窗: Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months)
OS was defined as the time from randomization to death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.
次要结局
- Percentage of Participants Who Died of Any Cause in PD-L1-Selected Population(Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months))
- OS in PD-L1-Selected Population(Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months))
- Percentage of Participants With PD as Determined by an Independent Review Committee (IRC) According to RECIST v1.1 or Death From Any Cause in ITT Population(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- PFS as Determined by an IRC According to RECIST v1.1 in ITT Population(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- Percentage of Participants With PD as Determined by an IRC According to RECIST v1.1 or Death From Any Cause in PD-L1-Selected Population(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- PFS as Determined by an IRC According to RECIST v1.1 in PD-L1-Selected Population(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by the Investigator According to RECIST v1.1 in Objective Response Rate (ORR)-Evaluable Population(Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 in DOR-Evaluable Population(Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- Percentage of Participants With an Objective Response of CR or PR as Determined by an IRC According to RECIST v1.1 in ORR-Evaluable Population(Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- DOR as Determined by an IRC According to RECIST v1.1 in DOR-Evaluable Population(Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- Percentage of Participants With PD as Determined by the Investigator According to Immune-Modified RECIST or Death From Any Cause in ITT Population(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- PFS as Determined by the Investigator According to Immune-Modified RECIST in ITT Population(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- Percentage of Participants With an Objective Response of CR or PR as Determined by the Investigator According to Immune-Modified RECIST in ORR-Evaluable Population(Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- DOR as Determined by the Investigator According to Immune-Modified RECIST in DOR-Evaluable Population(Baseline until documented CR/PR, PD, or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in ITT Population(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- PFS as Determined by the Investigator According to RECIST v1.1 in ITT Population(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- Percentage of Participants With PD as Determined by the Investigator According to RECIST v1.1 or Death From Any Cause in Participants With Sarcomatoid Histology(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- PFS as Determined by the Investigator According to RECIST v1.1 in Participants With Sarcomatoid Histology(Baseline until documented PD or death, whichever occurred first (until data cut-off date 29 September 2017, up to approximately 24 months))
- Percentage of Participants Who Died of Any Cause in Participants With Sarcomatoid Histology(Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months))
- OS in Participants With Sarcomatoid Histology(Baseline until death from any cause (until data cut-off date 14 February 2020, up to approximately 57 months))
- Change From Baseline in Symptom Interference as Determined by M.D. Anderson Symptom Inventory (MDASI) Part II Score(Baseline (Day 1 Cycle 1); Day 22 Cycle 1; Day 1 and 22 of every cycle from Cycle 2 up to Cycle 19; Cycle length = 42 days)
- Change From Baseline in Symptom Severity as Determined by MDASI Part I Score(Baseline; End of Treatment (EoT) visit (up to approximately 27 months))
- Change From Baseline in Symptom Severity as Determined by Brief Fatigue Inventory (BFI) Interference Scale Score(Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days)
- Change From Baseline in Symptom Severity as Determined by BFI Worst Fatigue Item(Baseline (Day 1 Cycle 1); every week for first 12 weeks, Days 1 and 22 of each cycle (Cycle 3 up to 19), within 30 days of PD (up to 27 months), at EoT (up to 27 months) and at 6, 12, 24, and 36 weeks after EoT (overall up to 27 months); 1 cycle=42 days)
- Change From Baseline in Treatment Side Effects Burden as Determined by Functional Assessment of Cancer Therapy Kidney Symptom Index (FKSI-19) General Population 5 (GP5) Item Score(Day 1 and 22 of every cycle (Baseline = Day 1 Cycle 1) up to Cycle 19; Cycle length = 42 days)
- Number of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab(Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycles 2, 4, and 8, and every eight cycles thereafter up to EoT [up to approximately 27 months] and 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days))
- Number of Participants With ATAs Against Bevacizumab(Baseline (Predose [Hour 0] at Day 1 Cycle 1); Post-Baseline (Predose at Cycle 3, at EoT [up to approximately 27 months] and at 120 days after EoT [up to approximately 27 months]) (Cycle length=42 days))
- Maximum Observed Serum Concentration (Cmax) for Atezolizumab(30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days))
- Minimum Observed Serum Concentration (Cmin) for Atezolizumab(Predose (Hour 0) on Day 22 of Cycle 1; predose (Hour 0) on Day 1 of Cycles 2; Cycle length = 42 days)
- Cmax for Bevacizumab(30 minutes after the end of bevacizumab infusion (atezolizumab infusion duration: 30-60 min; bevacizumab infusion duration: 30-90 minutes) on Day 1 of Cycle 1 (Cycle length = 42 days))
- Cmin for Bevacizumab(Pre-dose (Hour 0) on Day 1 of Cycle 3 (Cycle length = 42 days))