A Phase 3, Randomized, Double-blind, Study of Belzutifan + Zanzalintinib Versus Belzutifan + Placebo in Participants With Advanced RCC Who Have Progressed on or After Both PD-1/L1 and VEGF-TKI Therapies in Sequence or in Combination (LITESPARK-034)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 758
- 试验地点
- 91
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
Researchers are looking for new ways to treat advanced renal cell carcinoma (RCC).
A standard (usual) treatment for certain people with RCC is belzutifan (a study medicine), which is a targeted therapy. Targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. Researchers want to learn if adding another targeted therapy called zanzalintinib (another study medicine) can treat more people with advanced RCC than belzutifan alone.
The goal of this study is to learn if people who receive belzutifan and zanzalintinib live longer overall and without the cancer getting worse compared to people who receive belzutifan and placebo.
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
- •The main inclusion criteria include but are not limited to the following:
- •Has a histologically confirmed diagnosis of unresectable, advanced renal cell carcinoma (RCC) with clear cell component (with or without sarcomatoid features) ie, Stage IV RCC per American Joint Committee on Cancer (8th Edition)
- •Has measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
- •Has received no more than 3 prior systemic regimens for RCC, including only 1 prior anti-Programmed Cell Death-1/Programmed Cell Death 1 Ligand 1 therapy
排除标准
- •For exclusion criteria: The main exclusion criteria include but are not limited to the following:
- •Has any of the following: a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or required chronic supplemental oxygen
- •Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
- •Has 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
- •Has current pneumonitis/interstitial lung disease
- •Has a history of human immunodeficiency virus infection
- •Has Hepatitis B or Hepatitis C virus infection
- •Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Has a history of solid organ transplant
- •Has not adequately recovered from major surgery or has ongoing surgical complications
研究组 & 干预措施
Belzutifan + Placebo
Participants will receive 120 mg belzutifan orally and zanzalintinib-matching placebo once daily for approximately 24 months.
干预措施: Placebo (Drug)
Belzutifan + Zanzalintinib
Participants will receive 120 mg belzutifan orally and 60 mg zanzalintinib once daily for approximately 24 months.
干预措施: Belzutifan (Drug)
Belzutifan + Zanzalintinib
Participants will receive 120 mg belzutifan orally and 60 mg zanzalintinib once daily for approximately 24 months.
干预措施: Zanzalintinib (Drug)
Belzutifan + Placebo
Participants will receive 120 mg belzutifan orally and zanzalintinib-matching placebo once daily for approximately 24 months.
干预措施: Belzutifan (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to approximately 30 months
PFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first.
Overall Survival (OS)
时间窗: Up to approximately 50 months
OS is defined as the time from randomization to death due to any cause.
次要结局
- TTD in Disease Symptoms Using the FKSI-DRS (Items 1-9) Score(Up to approximately 25 months)
- Objective Response Rate (ORR)(Up to approximately 30 months)
- Duration of Response (DOR)(Up to approximately 30 months)
- Number of Participants Who Experience One or More Adverse Events (AEs)(Up to approximately 25 months)
- Number of Participants who Discontinue Study Treatment Due to an AE(Up to approximately 24 months)
- Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Baseline and up to approximately 25 months)
- Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score(Baseline and up to approximately 25 months)
- Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score(Baseline and up to approximately 25 months)
- Change From Baseline in Disease Symptoms Using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) (Items 1-9) Score(Baseline and up to approximately 25 months)
- Time to Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score(Up to approximately 25 months)
- TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score(Up to approximately 25 months)
- TTD in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Score(Up to approximately 25 months)