A Randomized, Double-Blind, Controlled Phase 3 Study of Cabozantinib in Combination With Nivolumab and Ipilimumab Versus Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma of Intermediate or Poor Risk
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Exelixis
- 入组人数
- 855
- 试验地点
- 159
- 主要终点
- Duration of Progression-Free Survival (PFS) by Blinded Independent Radiology Committee (BIRC)
研究概览
简要总结
This is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in combination with matched placebo. Approximately 840 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio at approximately 180 sites.
详细描述
This is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in combination with matched placebo. The primary objective of this study is to evaluate the effect of cabozantinib in combination with nivolumab and ipilimumab ("triplet") on the duration of progression-free survival (PFS) versus nivolumab and ipilimumab. A secondary objective is to evaluate the effect of triplet combination on the duration of overall survival (OS).
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
- Triple (Participant, Investigator, Outcomes Assessor)
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 advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component.
- •Intermediate- or poor-risk RCC as defined by International Metastatic RCC Database Consortium (IMDC) criteria.
- •Measurable disease per RECIST 1.1 as determined by the Investigator. Measurable disease must be outside the radiation field if radiation therapy was previously administered.
- •Karnofsky Performance Status (KPS) ≥ 70%.
- •Adequate organ and marrow function.
排除标准
- •Prior systemic anticancer therapy for unresectable locally advanced or metastatic RCC including investigational agents.
- •Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks prior to randomization.
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and stable for at least 4 weeks prior to randomization.
- •Concomitant anticoagulation with oral anticoagulants or platelet inhibitors.
- •Administration of a live, attenuated vaccine within 30 days prior to randomization.
- •Uncontrolled, significant intercurrent or recent illness including, but not limited to serious cardiovascular disorders (including uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment), GI disorders associated with high risk for perforation or fistula formation, tumors invading GI tract, bowel obstruction, intra-abdominal abscess, clinically significant bleeding events, cavitating pulmonary lesions, or lesions invading major pulmonary blood vessels.
- •Other clinically significant disorders such as:
- •Autoimmune disease that has been symptomatic or required treatment within the past two years from the date of randomization.
- •Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization.
- •Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active myobacterial infection.
- •Known history of COVID-19 unless the subject has clinically recovered from the disease at least 30 days prior to randomization.
- •Major surgery (eg, nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major or minor surgery before randomization.
- •Any other active malignancy at time of randomization or diagnosis of another malignancy within 3 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
研究组 & 干预措施
Experimental Arm
Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
干预措施: Cabozantinib (Drug)
Experimental Arm
Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
干预措施: Nivolumab (Biological)
Experimental Arm
Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
干预措施: Ipilimumab (Biological)
Control Arm
Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab
干预措施: Nivolumab (Biological)
Control Arm
Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab
干预措施: Ipilimumab (Biological)
Control Arm
Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab
干预措施: Cabozantinib-matched placebo (Drug)
结局指标
主要结局
Duration of Progression-Free Survival (PFS) by Blinded Independent Radiology Committee (BIRC)
时间窗: Up to 32 months
Duration of PFS was defined as the time from randomization to the earlier of either the date of radiographic progression per BIRC or the date of death due to any cause. PFS (months) = (earliest date of progression, death, censoring - date of randomization + 1)/30.4375. PFS was determined as per Response Evaluation Criteria in Solid Tumors version (RECIST) v1.1.
次要结局
- Duration of Overall Survival (OS)(Up to 58 months)