A Phase 2, Randomized, Active-controlled, Open-label, Multicenter Study of Belzutifan Plus Fulvestrant in Participants With Estrogen Receptor Positive, HER2 Negative Unresectable Locally Advanced or Metastic Breast Cancer After Progression on Previous Endocrine Therapy (LITESPARK-029)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 78
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of belzutifan (MK-6482) plus fulvestrant compared to everolimus plus endocrine therapy (ET) (investigator's choice of fulvestrant or exemestane) in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) unresectable metastatic breast cancer. There is no formal hypothesis testing in this study.
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
- •Has a diagnosis of estrogen receptor positive (ER+)/human epidermal growth factor receptor negative (HER2-) invasive breast carcinoma that is either locally advanced disease not amenable to resection or metastatic disease not treatable with curative intent
- •Has documented radiographic confirmation of disease progression during or after the last administered endocrine therapy (ET)
- •Provides additional tissue from the same sample used to determine ER and HER2 status locally
- •Has received ET in the noncurative setting and has 1) Radiographic disease progression on 12 months or more of ET in combination with CDK4/6 inhibitor in the noncurative setting or 2) Received at least 2 lines of ET in the noncurative setting including CDK4/6 inhibitor where the CDK 4/6 inhibitor was discontinued due to intolerance
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
- •Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible
- •Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks prior to the first dose of study intervention and have undetectable HBV viral load prior to randomization
排除标准
- •Has Breast cancer amenable to treatment with curative intent
- •Is unable to receive any of the endocrine therapies (ETs) (ie, fulvestrant or exemestane)
- •Has known difficulty in tolerating oral medications, unable to swallow orally administered medication, or conditions which would impair absorption of oral medications such as uncontrolled nausea or vomiting (ie, CTCAE =Grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction, motility disorder, malabsorption syndrome, or prior gastric bypass
- •Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications
- •Has active, bleeding diathesis, or on oral anti-vitamin K medication
- •Has history of noninfectious pneumonitis/interstitial lung disease including radiation pneumonitis that required steroids or has current pneumonitis/interstitial lung disease
- •Has a known germline BRCA mutation (deleterious or suspected deleterious) and has received previous treatment with poly-ADP ribose polymerase (PARP) inhibition either in the adjuvant or metastatic setting
- •Has received prior fulvestrant in the adjuvant, unresectable locally advanced, or metastatic setting
- •Has received any line of cytotoxic chemotherapy or PARP inhibitor in the unresectable or noncurative advanced/metastatic setting
- •Has received prior radiotherapy for non-central nervous system (CNS) disease or required corticosteroids for radiation-related toxicities including radiation pneumonitis, within 14 days of the first dose of study intervention
- •Is currently receiving either a strong inhibitor or inducer of CYP3A4 that cannot be discontinued for the duration of the study
- •Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization
- •Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
- •Has concurrent active Hepatitis B and Hepatitis C virus infection
- •Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study medication administration, or New York Heart Association Class III or Class IV congestive heart failure
- •Has not adequately recovered from major surgery or have ongoing surgical complications
研究组 & 干预措施
Belzutifan + Fulvestrant
Participants will receive belzutifan 120 mg orally once daily (QD) PLUS fulvestrant 500 mg via intramuscular (IM) injection on Days 1 and 15 of Cycle 1, and Day 1 of each 28-day cycle thereafter until progressive disease or discontinuation.
干预措施: Belzutifan (Drug)
Everolimus + ET (fulvestrant or exemestane)
Participants will receive everolimus 10 mg orally QD PLUS investigator's choice of fulvestrant 500 mg via IM injection on Days 1 and 15 of Cycle 1, and Day 1 of each 28-day cycle thereafter OR exemestane 25 mg orally QD until progressive disease or discontinuation.
干预措施: Everolimus (Drug)
Everolimus + ET (fulvestrant or exemestane)
Participants will receive everolimus 10 mg orally QD PLUS investigator's choice of fulvestrant 500 mg via IM injection on Days 1 and 15 of Cycle 1, and Day 1 of each 28-day cycle thereafter OR exemestane 25 mg orally QD until progressive disease or discontinuation.
干预措施: Exemestane (Drug)
Belzutifan + Fulvestrant
Participants will receive belzutifan 120 mg orally once daily (QD) PLUS fulvestrant 500 mg via intramuscular (IM) injection on Days 1 and 15 of Cycle 1, and Day 1 of each 28-day cycle thereafter until progressive disease or discontinuation.
干预措施: Fulvestrant (Drug)
Everolimus + ET (fulvestrant or exemestane)
Participants will receive everolimus 10 mg orally QD PLUS investigator's choice of fulvestrant 500 mg via IM injection on Days 1 and 15 of Cycle 1, and Day 1 of each 28-day cycle thereafter OR exemestane 25 mg orally QD until progressive disease or discontinuation.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to approximately 29 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.
次要结局
- Progression-free Survival (PFS) at 6 months(Up to approximately 29 months)
- Progression-free Survival (PFS) at 12 months(Up to approximately 29 months)
- Overall Survival (OS)(Up to approximately 29 months)
- Objective Response Rate (ORR)(Up to approximately 29 months)
- Clinical Benefit Rate (CBR)(Up to approximately 29 months)
- Number of Participants Who Experience an Adverse Event (AE)(Up to approximately 46 months)
- Number of Participants Who Discontinue Study Treatment Due To an AE(Up to approximately 46 months)