A Phase II, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Administered as Monotherapy or in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 305
- 试验地点
- 45
- 主要终点
- Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population
研究概览
简要总结
This multicenter, randomized, open-label study will evaluate the efficacy, safety and tolerability of atezolizumab as monotherapy or in combination with bevacizumab versus sunitinib in participants with histologically confirmed, inoperable, locally advanced or metastatic renal cell carcinoma who have not received prior systemic 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
- •Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting
- •Measurable disease, as defined by RECIST v1.1
- •Karnofsky performance score greater than or equal to (>/=) 70
- •Adequate hematologic and end-organ function as defined by protocol
- •Women of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective methods of contraception as defined by protocol
排除标准
- •Disease-Specific Exclusions:
- •Radiotherapy for renal cell carcinoma within 14 days prior to Cycle 1, Day 1 with the exception of single-fraction radiotherapy given for the indication of pain control
- •Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- •Uncontrolled hypercalcemia or symptomatic hypercalcemia
- •Malignancies other than renal cell carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome
- •General Medical Exclusions:
- •Life expectancy of less than (<) 12 weeks
- •Pregnant and lactating women
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- •History of autoimmune disease
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- •Participants with active or chronic hepatitis B, active hepatitis C, Human Immunodeficiency Virus (HIV) positive test, significant cardiovascular disease
- •Prior allogeneic stem cell or solid organ transplant
- •Exclusion Criteria Related to Medications:
- •Prior treatment with Cluster of Differentiation 137 (CD137) agonists, anti-Cytotoxic T-Lymphocyte Antigen-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- •Treatment with systemic immunostimulatory agents for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
- •Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1
- •Bevacizumab- and Sunitinib-Specific Exclusions:
- •Inadequately controlled hypertension
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •New York Heart Association Class II or greater congestive heart failure
- •History of myocardial infarction or unstable angina, stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1
研究组 & 干预措施
Atezolizumab and Bevacizumab
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) will be administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Atezolizumab and Bevacizumab
Atezolizumab 1200 milligrams (mg) and bevacizumab 15 milligrams per kilogram (mg/kg) will be administered as intravenous (IV) infusions every 3 weeks (q3w) on Day 1 and Day 22 of each 6-week cycle until disease progression.
干预措施: Bevacizumab (Drug)
Atezolizumab
Atezolizumab 1200 mg will be administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except European Union [EU] participants) can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Atezolizumab
Atezolizumab 1200 mg will be administered as IV infusion q3w on Day 1 and Day 22 of each 6-week cycle until disease progression. Upon disease progression, participants (except European Union [EU] participants) can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
干预措施: Bevacizumab (Drug)
Sunitinib
Sunitinib 50 mg will be administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
干预措施: Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody (Drug)
Sunitinib
Sunitinib 50 mg will be administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
干预措施: Bevacizumab (Drug)
Sunitinib
Sunitinib 50 mg will be administered orally once daily on Days 1 to 28 of each 6-week cycle until disease progression. Upon disease progression, participants can crossover to receive atezolizumab and bevacizumab combination until disease progression, lack of clinical benefit, unacceptable toxicity, withdrawal from study, or study completion or termination.
干预措施: Sunitinib (Drug)
结局指标
主要结局
Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Immune Cell 1/2/3 (IC1/2/3) Population
时间窗: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Percentage of Participants With Disease Progression Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Via Independent Review Committee (IRC) Assessment or Death in Intent-to-Treat (ITT) Population
时间窗: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
Progressive Disease (PD): at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 millimeters (mm); appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Progression-Free Survival (PFS) Per RECIST v1.1 Via IRC Assessment in ITT Population
时间窗: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
PFS Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population
时间窗: From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years)
PFS was defined as the time from randomization to the first occurrence of PD or death due to any cause. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions. Kaplan-Meier methodology was used to estimate PFS.
次要结局
- PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- PFS Per RECIST v1.1 Via Investigator Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Objective Response Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than Median Expression of an Immune Gene Signature(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in ITT Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Disease Progression Per RECIST v1.1 Via IRC Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- PFS Per RECIST v1.1 Via IRC Assessment in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Participants Who Have Tumors With Higher Than the 33rd Percentile Expression of an Immune Gene Signature(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- PFS Per RECIST v1.1 Via Investigator Assessment in ITT Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in IC1/2/3 Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- PFS Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]) Per RECIST v1.1 Via IRC Assessment in ITT Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in ITT Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Disease Progression Per RECIST v1.1 Via Investigator Assessment or Death in Crossover Population(From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Cmin of Bevacizumab(For Atezolizumab and Bevacizumab Arm: at First-line treatment discontinuation (up to approximately 2.75 years); For Crossover Arms: pre-infusion (0 hour) on Day 1 of Cycle 2 (1 cycle=6 weeks) (infusion length=30-90 minutes))
- Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in ITT Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Objective Response Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- PFS Per Modified RECIST Via Investigator Assessment in ITT Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in IC1/2/3 Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Disease Progression Per Modified RECIST Via Investigator Assessment or Death in ITT Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- PFS Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population(From randomization until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Duration of Response (DOR) Per RECIST v1.1 Via IRC Assessment in ITT Population(From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- DOR Per RECIST v1.1 Via Investigator Assessment in ITT Population(From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- DOR Per RECIST v1.1 Via IRC Assessment in IC1/2/3 Population(From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- DOR Per RECIST v1.1 Via Investigator Assessment in IC1/2/3 Population(From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- DOR Per Modified RECIST Via Investigator Assessment in ITT Population(From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- OS in IC1/2/3 Population(Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Objective Response Per RECIST v1.1 Via Investigator Assessment in Crossover Population(From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Maximum Serum Concentration (Cmax) of Atezolizumab(30 minutes after end of infusion on Cycle 1 Day 1 (1 cycle=6 weeks) (infusion length for first dose=60 minutes))
- Cmax of Bevacizumab(30 minutes after end of infusion on Day 1 of Cycles 1 and 2 (1 cycle=6 weeks) (infusion length=30-90 minutes))
- DOR Per Modified RECIST Via Investigator Assessment in IC1/2/3 Population(From CR or PR until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants Who Died in ITT Population(Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Overall Survival (OS) in ITT Population(Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- DOR Per RECIST v1.1 Via Investigator Assessment in Crossover Population(From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Minimum Serum Concentration (Cmin) of Atezolizumab(Pre-infusion (0 hour) on Day 1 of Cycles 2 and 4; Day 22 of Cycles 1, 2, and 4 (1 cycle=6 weeks) (infusion length=30-60 minutes))
- M.D. Anderson Symptom Inventory (MDASI) Interference Score(Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks))
- Percentage of Participants Who Died in IC1/2/3 Population(Randomization until death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- PFS Per RECIST v.1.1 Via Investigator Assessment in Crossover Population(From start of crossover treatment until disease progression or death due to any cause (until data cut-off date 17 October 2016, up to approximately 2.75 years))
- Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Atezolizumab(Cycle 1 Day 1 until treatment discontinuation (until data cut-off date 17 October 2016, up to approximately 2.75 years) (1 cycle=6 weeks))
- Brief Fatigue Inventory (BFI) Fatigue Level Score(Days 1 and 22 of Cycles 1 to 24; Day 1 of Cycle 25; treatment discontinuation (up to approximately 2.75 years) (1 cycle=6 weeks))