A Phase 3, Randomized, Open-label Study of Belzutifan + Zanzalintinib Versus Cabozantinib in Participants With Advanced RCC Who Experienced Disease Recurrence During or After Prior Adjuvant Anti-PD-1/L1 Therapy (LITESPARK-033)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 904
- 试验地点
- 150
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
Researchers are looking for more ways to treat advanced renal cell carcinoma (RCC) that is recurrent. Researchers want to learn if recurrent advanced renal cell carcinoma (RCC) responds (gets smaller or goes away) after treatment with belzutifan (MK-6482) and zanzalintinib compared to cabozantinib.
The goal of this study is to learn if:
People who take belzutifan and zanzalintinib live longer overall and without the cancer getting worse than people who take cabozantinib.
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
- •The main inclusion criteria include but are not limited to the following:
- •Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition)
- •Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
- •Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy
- •Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, new-onset angina, pulmonary embolism, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
- •Had deep vein thrombosis within 3 months before randomization unless stable, asymptomatic, and treated with therapeutic anticoagulation for at least 4 weeks before randomization
- •Has a left ventricular ejection fraction ≤50% or below the institutional (or local laboratory) normal range as determined by multigated acquisition or echocardiogram
- •Has had major surgery within 8 weeks before randomization or has not adequately recovered from major surgery or has ongoing surgical complications
- •Has current pneumonitis/interstitial lung disease
- •Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic chest pain), ascites, or pericardial fluid requiring drainage within 4 weeks prior to randomization
- •Has a gastrointestinal disorder including those associated with a high risk of perforation or fistula formation
- •Has a serious active nonhealing wound/ulcer/bone fracture
- •Has a requirement for hemodialysis or peritoneal dialysis
- •Has history of human immunodeficiency virus infection
- •Has hepatitis B or hepatitis C virus
- •Has pharmacologically uncompensated, symptomatic hypothyroidism
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
研究组 & 干预措施
Belzutifan plus Zanzalintinib
Participants will receive belzutifan orally once daily (QD) PLUS zanzalintinib orally QD until one of the reasons for discontinuation of study intervention are met.
干预措施: Belzutifan (Drug)
Cabozantinib
Participants will receive cabozantinib orally QD until one of the reasons for discontinuation of study intervention are met.
干预措施: Cabozantinib (Drug)
Belzutifan plus Zanzalintinib
Participants will receive belzutifan orally once daily (QD) PLUS zanzalintinib orally QD until one of the reasons for discontinuation of study intervention are met.
干预措施: Zanzalintinib (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Up to approximately 73 months
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.
Overall Survival (OS)
时间窗: Up to approximately 73 months
OS is defined as the time from randomization to death due to any cause.
次要结局
- Objective Response Rate (ORR)(Up to approximately 73 months)
- Duration of Response (DOR)(Up to approximately 73 months)
- Number of Participants Who Experience One or More Adverse Events (AEs)(Up to approximately 73 months)
- Number of Participants Who Discontinue Study Treatment due to an AE(Up to approximately 73 months)
- Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Global Health/Health-Related Quality of Life (HRQoL) Items 29 and 30 Combined Score(Up to approximately 25 months)
- Change From Baseline in EORTC QLC-C30 Physical Functioning Items 1-5 Score(Up to approximately 25 months)
- Change From Baseline in EORTC QLQ-C30 Role Functioning Items 6-7 Score(Up to approximately 25 months)
- Change From Baseline in Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score(Up to approximately 25 months)
- Time From Baseline to First Deterioration in EORTC-QLC-C30 Global Health/HRQoL Score(Up to approximately 25 months)
- Time From Baseline to First Deterioration in EORTC-QLC-C30 Physical Functioning Score(Up to approximately 25 months)
- Time From Baseline to First Deterioration in EORTC-QLC-C30 Role Functioning Score(Up to approximately 25 months)
- Time From Baseline to First Deterioration in FKSI-DRS Score(Up to approximately 25 months)