NCT04586231进行中（未招募）3 期
An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 747
- 试验地点
- 184
- 主要终点
- Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy.
The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.
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, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
- •Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose.
- •Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.
- •Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
- •Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease
- •Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/metastatic RCC.
- •A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.
- •A female participant is eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.
- •Adequately controlled blood pressure.
- •Adequate organ function.
排除标准
- •A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
- •Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Clinically significant cardiac disease within 6 months of first dose of study intervention.
- •Prolongation of QTc interval to >480 ms.
- •Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.
- •Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.
- •Moderate to severe hepatic impairment.
- •History of significant bleeding within 3 months before randomization.
- •History of solid organ transplantation.
- •Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
- •Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
- •Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
- •Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization.
- •Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor.
- •Prior treatment with lenvatinib.
- •Prior treatment with cabozantinib.
- •Currently participating in a study of an investigational agent or using an investigational device.
- •Active infection requiring systemic therapy.
- •History of human immunodeficiency virus (HIV) infection.
- •History of hepatitis B or known active hepatitis C infection.
研究组 & 干预措施
Belzutifan + Lenvatinib
Experimental
Belzutifan 120 mg and lenvatinib 20 mg orally once a day
干预措施: Lenvatinib (Drug)
Cabozantinib
Active Comparator
Cabozantinib 60 mg orally once a day
干预措施: Cabozantinib (Drug)
Belzutifan + Lenvatinib
Experimental
Belzutifan 120 mg and lenvatinib 20 mg orally once a day
干预措施: Belzutifan (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 34 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. Per 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 will be presented.
Overall Survival (OS)
时间窗: Up to approximately 44 months
OS is defined as time from randomization to death due to any cause.
次要结局
- Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)(Up to approximately 44 months)
- Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)(Up to approximately 24 months)
- Number of Participants Who Experienced One or More Adverse Events (AEs)(Up to approximately 44 months)
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)(Up to approximately 44 months)
研究者
研究点 (184)
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