monarcHER: A Phase 2, Randomized, Multicenter, 3-Arm, Open-Label Study to Compare the Efficacy of Abemaciclib Plus Trastuzumab With or Without Fulvestrant to Standard-of-Care Chemotherapy of Physician's Choice Plus Trastuzumab in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 237
- 试验地点
- 34
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate the effectiveness of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus physicians choice standard of care chemotherapy in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+) locally advanced or metastatic breast cancer after prior exposure to at least two HER2-directed therapies for advanced disease.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •diagnosis of HR+, HER2+ breast cancer (BC)
- •unresectable locally advanced recurrent BC or metastatic BC
- •adequate tumor tissue available prior to randomization
- •measurable and/or non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •previously received:
- •at least 2 HER2-directed therapies for advanced disease
- •participant must have received trastuzumab emtansine (T-DM1) in any disease setting
- •must have received a taxane in any disease setting
- •may have received any endocrine therapy (excluding fulvestrant)
- •have postmenopausal status due to surgical / natural menopause or chemical ovarian suppression
- •performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group scale
- •left ventricular ejection fraction (LVEF) of 50% or higher at baseline
- •adequate organ function
- •negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib if menopause induced by gonadotropin-releasing hormone (GnRH) agonist or radiation
- •discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture at least 2 weeks prior to randomization and recovered from the acute effects of therapy
- •discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and endocrine therapy), except trastuzumab, for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy
- •are able to swallow capsules
排除标准
- •have visceral crisis
- •known central nervous system (CNS) metastases that are untreated, symptomatic, or require steroids to control symptoms
- •had major surgery within 14 days prior to randomization
- •received prior treatment with any cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor
- •received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of randomization for a nonmyelosuppressive or myelosuppressive agent, respectively
- •have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study
- •history within the last 6 months of symptomatic congestive heart failure, myocardial infarction, or unstable angina
- •history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
- •history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years
- •active bacterial, fungal infection, or detectable viral infection
- •have received any recent (within 28 days prior to randomization) live virus vaccination
- •hypersensitivity to trastuzumab, murine proteins, fulvestrant, or to any of the excipients
研究组 & 干预措施
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant
150 milligram (mg) abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 milligram per kilogram (mg/kg) trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500 mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.
干预措施: Abemaciclib (Drug)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant
150 milligram (mg) abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 milligram per kilogram (mg/kg) trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500 mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.
干预措施: Trastuzumab (Drug)
150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant
150 milligram (mg) abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 milligram per kilogram (mg/kg) trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500 mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.
干预措施: Fulvestrant (Drug)
150 mg Abemaciclib + 8 mg/kg Trastuzumab
150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.
干预措施: Abemaciclib (Drug)
150 mg Abemaciclib + 8 mg/kg Trastuzumab
150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.
干预措施: Trastuzumab (Drug)
8 mg/kg Trastuzumab + Standard of Care Chemotherapy
8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label
干预措施: Trastuzumab (Drug)
8 mg/kg Trastuzumab + Standard of Care Chemotherapy
8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label
干预措施: Standard of Care Single Agent Chemotherapy (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Baseline to Progressive Disease or Death from Any Cause (Up To 36 Months)
PFS time was measured from the date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
次要结局
- Percentage of Participants With 1 Year Overall Survival (OS)(Randomization to date of death from any cause assessed at 1 year)
- Percentage of Participants With 2 Year OS(Randomization to date of death from any cause assessed at 2 years)
- Percentage of Participants With 3 Year OS(Randomization to date of death from any cause assessed at 3 years)
- Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)(Baseline to Objective Disease Progression (Up To 36 Months))
- Duration of Response (DoR)(Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up To 36 Months))
- Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)(Baseline to Objective Disease Progression (Up To 36 Months))
- Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months: Clinical Benefit Rate (CBR)(Date of CR, PR or SD to 6 Months Post CR, PR or SD (Up To 36 Months))
- Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)(Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months))
- Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)(Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months))
- Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score(Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months))
- Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)(Baseline, 30 Days After Treatment Discontinuation (Up To 36 Months))
- Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and Its Metabolites (M2 and M20)(Cycle(C)1 Day(D)1,C1D15, C2D1, C2D8, C3D1,C3D15, C4D1, C5D1:pre-dose; C1D1, C2D1, C3D1, C4D1, C5D1:post-dose)