临床试验/NCT05696626

NCT05696626招募中3 期

An Open Label, Randomized, Multicenter Study Comparing the Efficacy and Safety of the Combination of Lasofoxifene and Abemaciclib to the Combination of Fulvestrant and Abemaciclib for the Treatment of Pre- and Postmenopausal Women and Men With Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

LeonaBio421 个研究点分布在 4 个国家目标入组 600 人开始时间: 2023年10月31日最近更新: 2026年6月22日

适应症

干预措施

试验速览

阶段: 3 期
状态: 招募中
发起方: LeonaBio
入组人数: 600
试验地点: 421
主要终点: Progression free survival (PFS)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib for the treatment of pre- and postmenopausal women and men who have previously received ribociclib or palbociclib-based treatment and have locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation.

The main question the study aims to answer is:

• To compare the efficacy of the combination of lasofoxifene and abemaciclib with that of fulvestrant and abemaciclib Participants will receive either receive 5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day or the combination of fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day.

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

•Pre- or postmenopausal women or men.
•Locally advanced and/or metastatic ER+ breast cancer with radiological or clinical evidence of progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease.
•Histological or cytological confirmation of ER+/HER2 - disease
•No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer.
•At least 1 or more ESR1 point mutations in the ESR1 ligand binding domain as assessed in cell- free ctDNA obtained from a blood or breast cancer tissue.
•Locally advanced or metastatic breast cancer with at least 1 measurable (according to RECIST 1.1) lesion with or without non-measurable lesions.
•Subjects may have received 1 cytotoxic chemotherapy regimen in the metastatic disease setting prior to study entry, but must have recovered from chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy.
•Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
•Adequate organ function
•Able to swallow tablets
•Brain metastases are allowed only if the following 4 parameters hold:
•Asymptomatic,
•Definitively treated (e.g., radiotherapy, surgery),
•Not requiring steroids up to 4 weeks before study treatment initiation, AND
•Central nervous system disease stable for >3 months prior to registration as documented by magnetic resonance imagining (MRI).
•Able to understand and voluntarily sign a written informed consent before any screening procedures.
•Every attempt should be made to obtain a biopsy of metastatic breast cancer tissue, when safe and feasible, to provide histological or cytological confirmation of ER+/HER2- disease as assessed by a local laboratory, according to American Society of Clinical Oncology/College of American Pathologists guidelines, using slides, paraffin blocks, or paraffin samples. If a biopsy is done, it may undergo genomic testing at some point to assess for ESR1 mutations and correlation with ctDNA results. If a biopsy is not possible or inappropriate from a clinical standpoint, the ER and HER2 status from the subject's most recent biopsy must confirm that the subject is ER+ and HER2

排除标准

•Lymphangitic carcinomatosis involving the lung.
•History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy.
•Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator.
•Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy.
•Subjects with a known hypersensitivity to fulvestrant or to any of the excipients
•Radiotherapy within 30 days prior to Visit 0 (Day 1) except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to Visit 0 (Day 1). Subjects must have recovered from radiotherapy toxicities prior to Visit 0 (Day 1).
•Known RB1 mutations or deletions that in the opinion of the investigator confer resistance to CDK4/6i. (Screening for RB1 mutation is not required for entry.)
•History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of >480 msec.
•History of a pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia, unless the event occurred greater than 6 months prior to screening and the subject is treated with chronic anticoagulant therapy such as apixaban (Eliquis) or rivaroxaban (Xarelto).
•Lasofoxifene is not recommended for use in subjects with conditions that place them at increased risk for VTEs (such as severe congestive heart failure [CHF] or prolonged immobilization).
•On concomitant strong CYP3A4 inhibitors.
•On strong and moderate CYP3A4 inducers.
•Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption.
•Active systemic bacterial or fungal infection (requiring intravenous [IV] antibiotics or antifungals at the time of initiating study treatment).
•Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
•History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery.
•Positive serum pregnancy test (only if premenopausal).
•Sexually active premenopausal women and men unwilling to use double-barrier contraception.
•Women who are breast feeding
•History of non-compliance to medical regimens.
•Unwilling or unable to comply with the protocol.
•Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.
•Subjects with a history of familial hypertriglyceridemia or fasting triglyceride levels >880 mg/dL at screening.
•Fasting triglyceride level >300 mg/dL and ≤880 mg/dL at screening. Subjects may be retested and enrolled if they have a repeat fasting triglyceride level less than or equal to 300 mg/dL prior to enrollment (e.g., after adjustment with diet and/or treatment).
•Fasting cholesterol level >400 mg/dL at screening. Subjects may be retested and enrolled if they have a repeat fasting cholesterol level less than or equal to 400 mg/dL prior to enrollment (e.g., after adjustment with diet and/or treatment).

研究组 & 干预措施

Reference Therapy

Active Comparator

Pre- and Postmenopausal Women and Men with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease and who have an ESR1 mutation.

干预措施: Fulvestrant in combination with abemaciclib (Drug)

Treatment

Experimental

干预措施: Lasofoxifene in combination with abemaciclib (Drug)

结局指标

主要结局

Progression free survival (PFS)

时间窗: Within approximately 3 years

PFS is defined as the time from the date of randomization \[Visit 0 (Day 1)\] to the earliest date of first documented progression per RECIST 1.1 as determined by BICR or death due to any cause.

次要结局

Time to cytotoxic chemotherapy(Within approximately 3 years)
Overall survival (OS)(Within approximately 3 years)
Clinical benefit rate (CBR)(Within approximately 3 years)
Duration of response (DoR) in subjects with an objective response(Within approximately 3 years)
Objective response rate (ORR)(Within approximately 3 years)
Time to response (TTR) in subjects with an objective response(Within approximately 3 years)
Quality of Life (QoL) evaluated using the Functional Assessment of Cancer Therapy-Breast Cancer-Endocrine Subscale (FACT B-ES)(Within approximately 3 years)
Incidence of Adverse Events (AEs) and Serious AEs(Within approximately 3 years)

研究者

发起方

LeonaBio

申办方类型

Industry

责任方

Sponsor

研究点 (421)

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