NCT06982521招募中3 期
A Phase 3 Open-Label Randomized Study Assessing the Efficacy and Safety of RLY-2608 + Fulvestrant Versus Capivasertib + Fulvestrant as Treatment for PIK3CA-mutant Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Locally Advanced or Metastatic Breast Cancer Following Recurrence or Progression On or After Treatment With a CDK4/6 Inhibitor
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 540
- 试验地点
- 259
- 主要终点
- Progression-Free Survival (PFS) within the overall and kinase population by blinded independent central review (BICR)
研究概览
简要总结
This is a global, multicenter, open-label, randomized Phase 3 study comparing the efficacy and safety of RLY-2608 (zovegalisib) + fulvestrant to capivasertib + fulvestrant for the treatment of patients with HR+/HER2- ABC with PIK3CA mutation following recurrence or progression on or after treatment with a CDK4/6 inhibitor.
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
- •Patient has ECOG performance status of 0-1
- •One or more known primary oncogenic PIK3CA mutation(s)
- •Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and peri-menopausal) women can be enrolled if amenable to treatment with a gonadotropin-releasing hormone (GnRH) agonist. Patients are to have commenced treatment with a GnRH agonist at least 2 weeks prior to randomization and must be willing to continue on it for the duration of the study.
- •Histologically or cytologically confirmed diagnosis of HR+/HER2- locally advanced or metastatic breast cancer (ABC) with radiological or objective evidence of recurrence or progression; locally advanced disease must not be amenable to resection with curative intent
- •Measurable disease per RECIST v1.1 or evaluable bone-only disease.
- •Must have radiological evidence of progression on or after previous treatment for HR+/HER2- ABC with:
- •At least 1 and no more than 2 lines of endocrine therapy (ET) in the (neo)adjuvant setting with recurrence on or within 12 months of completion or in the ABC setting
- •Only 1 prior line of CDK4/6 inhibitor therapy in one of the following settings:
- •CDK4/6 inhibitor + ET in the ABC setting
- •CDK4/6 inhibitor therapy in the adjuvant setting if progression occurred during or within 12 months of completion of adjuvant CDK4/6 inhibitor with ET
- •Patients who progressed during or within 12 months of completion of adjuvant CDK4/6 inhibitor and after receiving CDK4/6 inhibitor therapy in the advanced setting are considered to have had >1 prior line of CDK4/6 inhibitor and are not eligible
排除标准
- •Prior treatment with any of the following:
- •CDK2 inhibitors. Prior treatment with other investigational CDK inhibitors could be permitted upon discussion and approval from the Sponsor
- •PIK3, AKT, or mTOR inhibitors or any agent whose mechanism of action is the inhibit the PIK3/AKT/mTOR pathway
- •Immunotherapy
- •Antibody drug conjugates
- •Type 1 diabetes, or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose ≥ 140 mg/dL (7.8 mmol/L), or glycosylated hemoglobin (HbA1c) ≥7.0% (≥ 53 mmol/mol).
- •Clinically significant, uncontrolled cardiovascular disease
- •Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
- •Known active uncontrolled or symptomatic CNS metastases associated with progressive neurological symptoms or requiring ongoing corticosteroids or anticonvulsants for symptomatic control
- •Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
- •History of hypersensitivity to fulvestrant or drugs in a similar class as fulvestrant, zovegalisib, or capivasertib, including their excipients
- •Known activating AKT mutations, loss-of-function PTEN mutations, or loss of PTEN expression resulting in oncogenic pathway activation downstream of PI3K
研究组 & 干预措施
Zovegalisib + fulvestrant
Experimental
Zovegalisib + fulvestrant combination for participants with HR+/HER2- advanced breast cancer
干预措施: Zovegalisib (Drug)
Zovegalisib + fulvestrant
Experimental
Zovegalisib + fulvestrant combination for participants with HR+/HER2- advanced breast cancer
干预措施: Fulvestrant (Drug)
capivasertib + fulvestrant
Active Comparator
capivasertib + fulvestrant combination for participants with HR+/HER2- advanced breast cancer
干预措施: Capivasertib (Drug)
capivasertib + fulvestrant
Active Comparator
capivasertib + fulvestrant combination for participants with HR+/HER2- advanced breast cancer
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) within the overall and kinase population by blinded independent central review (BICR)
时间窗: The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months
次要结局
- Duration of Response (DOR) within the overall and kinase populations(Up to approximately 77 months)
- Overall Survival (OS) within the overall and kinase populations(The time from randomization to the date of death by any cause, up to approximately 77 months)
- PFS by Investigator within the overall and kinase populations(The time from date of randomization until radiographic progression per RECIST v1.1, or death due to any cause, up to approximately 77 months)
- Objective Response Rate (ORR) within the overall and kinase populations(Up to approximately 77 months)
- Clinical Benefit Rate (CBR) within the overall and kinase populations(Up to approximately 77 months)
- Occurrence/frequency of Adverse Events (AEs) and its relationship to the study drugs (safety and tolerability) within the overall and kinase populations(Up to approximately 77 months)
- Plasma concentrations of RLY-2608 (and its metabolites as appropriate)(Approximately every 2 weeks in Cycle 1 (4-week cycle) and during Cycles 2 and 3)
- European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) scale/item scores including change from baseline and time to deterioration within overall and kinase populations(Up to approximately 77 months)
- EORTC Quality of Life Questionnaire Breast Cancer-Specific Module (EORTC QLQ-BR23) scale/item scores including change from baseline and time to deterioration within the overall and kinase populations(Up to approximately 77 months)
- Health state utility data for economic evaluation by EQ-5D-5L health state utility index within the overall and kinase populations(Up to approximately 77 months)
- Plasma concentrations of zovegalisib (and its metabolites as appropriate)(Approximately every 2 weeks in Cycle 1 (4-week cycle) and during Cycles 2 and 3)
研究者
研究点 (259)
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