An Open-label, Randomized, Non-comparative Phase 2 Study of ARV-471 or Anastrozole in Post-menopausal Women With ER+/HER2- Breast Cancer in the Neoadjuvant Setting
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Arvinas Inc.
- 入组人数
- 152
- 试验地点
- 1
- 主要终点
- Percent Reduction in Ki-67 Expression From Baseline to Day 15 in Tumor Biopsies
研究概览
简要总结
This trial is a Phase 2 neoadjuvant study evaluating ARV-471 or anastrozole in post-menopausal women with estrogen receptor positive/ human epidermal growth factor receptor 2 (ER+/HER2)- localized breast cancer.
详细描述
This is a Phase 2, open-label, randomized, non-comparative proof of concept study of ARV-471 or anastrozole in participants with ER+/HER2- breast cancer amenable to definitive surgical resection. The main goal of this study is to evaluate the biological activity of ARV-471 and anastrozole, respectively.
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
- •Post-menopausal females ≥ 18 years.
- •Histologically or cytologically confirmed ER+ and HER2- breast cancer (per local assessment). ER and HER2 status must be documented:
- •ER+ disease, with ER staining of ≥ 10% of tumor cell nuclei by immunohistochemistry (IHC) per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
- •HER2- disease by either IHC or in situ hybridization per ASCO/CAP guidelines.
- •Ki-67 score ≥ 5%, analyzed locally.
- •Clinical T1c-T4c, N0-N2, M0 breast cancer amenable to definitive surgical resection, without bilateral breast ductal carcinoma in situ or invasive breast cancer.
- •The primary tumor must be at least 1.5 cm by imaging.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Willingness to undergo a screening biopsy, an on-treatment biopsy and surgical resection.
排除标准
- •Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or cervical carcinoma in situ.
- •Any of the following in the previous 6 months: Myocardial infarction; Severe unstable angina; Coronary/peripheral artery bypass graft; Symptomatic congestive heart failure (New York Heart Association class III or IV); Cerebrovascular accident; Transient ischemic attack; Symptomatic pulmonary embolism or other clinically significant episode of thromboembolism.
- •Any of the following in the previous 6 months: Congenital long QT syndrome; Torsade de Pointes; Sustained ventricular tachyarrhythmia and ventricular fibrillation; Left anterior hemiblock (bifascicular block); Ongoing cardiac dysrhythmias of NCI CTCAE ≥ Grade 2; Atrial fibrillation of any grade (≥ Grade 2 in the case of asymptomatic lone atrial fibrillation).
- •corrected QT (Fridericia method) (QTcF) > 470 msec.
- •Active, uncontrolled bacterial, fungal or viral infection, including (but not limited to) hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
- •Active inflammatory gastrointestinal disease, chronic diarrhea, known uncontrolled diverticular disease, or previous gastric resection or lap band surgery.
- •Cirrhosis meeting criteria for Child Pugh B and C.
- •Prior treatment for breast cancer including systemic therapy (eg, chemotherapy, hormonal therapy), radiation, surgery, or any investigational agents.
- •Any live vaccines within 14 days of planned start of first dose of study drug.
- •Major surgery (as defined by the Investigator) within four weeks of first dose of study drug.
研究组 & 干预措施
Arm A: ARV-471 (Experimental)
Participants received 200 mg ARV-471 (2*100 mg tablets) once daily for approximately 5.5 months prior to undergoing surgical resection (no later than Cycle 6 Day 18 [C6D18] + 14 days).
干预措施: ARV-471 (Drug)
Arm A: ARV-471 (Experimental)
Participants received 200 mg ARV-471 (2*100 mg tablets) once daily for approximately 5.5 months prior to undergoing surgical resection (no later than Cycle 6 Day 18 [C6D18] + 14 days).
干预措施: Surgical resection of breast tumor (Procedure)
Arm B: Anastrozole
Participants received 1 mg Anastrozole tablet orally once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days).
干预措施: Anastrozole (Drug)
Arm B: Anastrozole
Participants received 1 mg Anastrozole tablet orally once daily for approximately 5.5 months prior to undergoing surgical resection (no later than C6D18 + 14 days).
干预措施: Surgical resection of breast tumor (Procedure)
结局指标
主要结局
Percent Reduction in Ki-67 Expression From Baseline to Day 15 in Tumor Biopsies
时间窗: Baseline (during screening, prior to Day 1) and Day 15
Tumor biopsy Ki-67 expression (% of tumor cells that are positive for Ki-67) at baseline and Cycle 1 Day 15 (C1D15) was collected. Ki-67 expression was assessed by immunohistochemical staining in a central laboratory. The log-transformed Ki-67 after approximately 2 weeks of treatment as a percentage of the baseline value, ie, the ratio between the Ki-67 measurements obtained from C1D15 visit and baseline was modelled using a generalized linear model (GLM) with both stratification factors (ie, baseline Ki-67 score and the tumor size) and treatment as co-variates. The treatment effects were back transformed into geometric means and their Confidence Intervals. The percent change, in other words, relative reduction, of Ki-67 after 2 weeks of treatment is reported as the complement of the ratio between the Ki-67 measurement from C1D15 and baseline, that is 100% × (1 - geometric mean ratio between Ki-67 at C1D15 and Ki-67 at baseline).
次要结局
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Study Drug Discontinuation(From signing of consent to minimum of 30 days after last administration of study drug (up to approximately 6.5 months))
- Pathologic Stage at the Time of Surgical Resection(At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days)
- Pathological Complete Response(pCR) Rate at the Time of Surgical Resection(At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days)
- Number of Participants With Modified Preoperative Endocrine Prognostic Index (mPEPI) Score of 0 at the Time of Surgical Resection(At Cycle 6 Day 18 (approximately 5.5 months), each cycle is 28 days)
- Breast Conserving Surgery (BCS) Rate(At Cycle 6 (from Day 141 to Day 168), each cycle is 28 days)
- Radiographic Response Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) in Primary Tumor During Cycle 6(At Cycle 6 (from Day 141 to Day 168), each cycle is 28 days)
- Percentage Change From Baseline at Cycle 6 Day 1 in Caliper Measurement of the Primary Tumor(Baseline (Day 1) and Cycle 6 Day 1 (At Day 141), each cycle is 28 days)