Fovinaciclib Plus Aromatase Inhibitors and Dual HER2 Blockade in a Response-Adapted Neoadjuvant Strategy for HR-Positive/HER2-Positive Early Breast Cancer (TAYLOR-003)
Fovinaciclib Plus Aromatase Inhibitors and Dual HER2 Blockade in a Response-Adapted Neoadjuvant Strategy for HR-Positive/HER2-Positive Early Breast Cancer (TAYLOR-003)
調査の概要
状態
詳細な説明
This is a prospective, response-adapted, phase II study designed to evaluate an individualized neoadjuvant treatment strategy based on fovinaciclib in combination with aromatase inhibitors and dual HER2 blockade in patients with HR-positive/HER2-positive early breast cancer. The study incorporates an adaptive treatment algorithm guided by early on-treatment assessment of tumor response, with the aim of optimizing therapeutic efficacy while minimizing unnecessary chemotherapy exposure.
All eligible patients initially receive neoadjuvant treatment with fovinaciclib plus endocrine therapy and HER2-targeted therapy according to the study protocol. Following completion of the predefined initial treatment phase, tumor response is assessed according to protocol-defined evaluation methods.
Patients who achieve an adequate response continue the same neoadjuvant regimen to complete the planned course of therapy. In contrast, patients demonstrating a suboptimal response are transitioned to standard neoadjuvant chemotherapy combined with HER2-targeted therapy prior to surgery. Postoperative treatment selection and management are conducted according to protocol-defined principles and investigator assessment.
By tailoring treatment intensity according to early response, the study seeks to maximize therapeutic benefit in responsive patients while facilitating timely treatment modification for those less likely to benefit from the initial regimen.
Primary and secondary objectives include evaluation of clinical efficacy, safety and tolerability of the response-adapted neoadjuvant strategy, and the feasibility of treatment modification based on early response assessment. Exploratory analyses will investigate potential biomarkers associated with treatment response and resistance, with the goal of informing future individualized treatment approaches.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Yunxiang Zhou
- 電話番号：15868131018
- メール：yxzhou@zju.edu.cn
研究場所
-
-
Jiangsu
-
Nanjing、Jiangsu、中国、210029
- 募集
- The First Affiliated Hospital of Nanjing Medical University
-
コンタクト：
- Xiaoan Liu
- 電話番号：025-83718836
- メール：liuxiaoan@126.com
-
主任研究者：
- Xiaoan Liu
-
-
Zhejiang
-
Hangzhou、Zhejiang、中国、310009
- 募集
- 2nd Affiliated Hospital, School of Medicine
-
主任研究者：
- Yiding Chen
-
コンタクト：
- Yunxiang Zhou
- 電話番号：15868131018
- メール：ydchen@zju.edu.cn
-
コンタクト：
-
Ningbo、Zhejiang、中国、315010
- 募集
- Ningbo No. 2 Hospital
-
主任研究者：
- Xujun Li
-
コンタクト：
- Wei Zhang
- 電話番号：13586562390
- メール：20949061@qq.com
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria Subjects voluntarily agree to participate in the study, fully understand the study procedures, provide written informed consent (ICF), and are willing and able to comply with all study procedures.
Female patients aged ≥18 years and ≤75 years. Histologically confirmed HR-positive (ER >10%) and HER2-positive (IHC 3+ or IHC 2+/ISH+) early-stage or locally advanced invasive breast cancer.
Pathologically staged as stage I-III according to the American Joint Committee on Cancer (AJCC) 8th edition staging system.
Premenopausal patients must receive ovarian function suppression. Considered suitable for aromatase inhibitor treatment according to investigator assessment.
Presence of evaluable disease according to RECIST version 1.1, including measurable and/or non-measurable lesions.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. Ability to swallow capsules.
Adequate bone marrow and organ function, defined as follows:
Absolute neutrophil count (ANC) ≥1.5 × 10^9/L; Hemoglobin ≥100 g/L (without red blood cell transfusion within 14 days prior to randomization); Platelet count ≥100 × 10^9/L; Total serum bilirubin ≤1.5 × upper limit of normal (ULN); patients with Gilbert syndrome must have total bilirubin ≤3 × ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN; Serum creatinine <1.5 × ULN or creatinine clearance ≥50 mL/min; Left ventricular ejection fraction (LVEF) ≥50%; QT interval ≤480 ms. Exclusion Criteria Current participation in another clinical trial involving investigational therapy, or participation in any other medical study considered scientifically or medically incompatible with this study.
Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer. History of uncontrolled seizures or central nervous system disease. History of other malignancies within the past 5 years. Pregnant or breastfeeding women. Known severe hypersensitivity to any component of the study drugs. Severe comorbidities, including uncontrolled hypertension (e.g., systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg), uncontrolled diabetes mellitus, or active infection. Patients with adequately controlled hypertension may be enrolled.
Clinically uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage or medical intervention within 2 weeks prior to first dosing.
Myocardial infarction within 6 months prior to first dosing; uncontrolled arrhythmia (QTc ≥470 ms, calculated using Fridericia's formula); New York Heart Association (NYHA) class III-IV heart failure; LVEF <50%; or clinically significant pleural effusion, pericardial effusion, or ascites requiring intervention.
Dysphagia, active gastrointestinal disease, history of major gastrointestinal surgery, malabsorption syndrome, or any condition that may affect absorption of study drugs.
Active hepatitis B infection [HBsAg-positive with detectable HBV-DNA], active hepatitis C infection [HCV antibody-positive with detectable HCV-RNA], positive syphilis screening (except confirmed inactive infection), known HIV infection, or positive HIV screening result.
Receipt of major surgery, radiotherapy, tumor immunotherapy, monoclonal antibody-based antitumor therapy, or other systemic antitumor therapies considered by the investigator to interfere with study treatment efficacy within 28 days prior to first dosing.
Planned or previous organ transplantation or bone marrow transplantation. Known history of psychiatric substance abuse or drug addiction. Any other condition that, in the investigator's judgment, would make the subject unsuitable for participation in the study.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Culmerciclib + AI +HP
fovinaciclib in combination with aromatase inhibitors and dual HER2 blockade
|
Letrozole or anastrozole
CDK4/6 inhibitor
dual HER2 blockade
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Total Pathological Complete Response (tpCR) Rate: ypT0/Tis, ypN0
時間枠：24 weeks
|
The tpCR rate is defined as the proportion of participants with no residual invasive cancer cells in both the breast primary tumor site (residual in situ cancer cells are permitted) and all sampled axillary lymph nodes.
|
24 weeks
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
イベントフリーサバイバル（EFS）
時間枠：約5年
|
EFSは、ランダム化から次のイベントのいずれかまでの時間として定義されます。手術、局所的または遠い再発、2番目の主要な悪性腫瘍、または原因による死亡。
|
約5年
|
|
有害事象（AE）
時間枠：約3年
|
AEは、因果関係を推定することなく、研究介入に一時的に関連する薬用製品を投与した研究参加者の厄介な医学的発生として定義されます。
|
約3年
|
|
Breast Pathological Complete Response (bpCR) Rate: ypT0/Tis
時間枠：24 weeks
|
The bpCR rate is defined as the proportion of participants with no residual invasive cancer cells in the breast primary tumor site (residual in situ cancer cells are permitted).
|
24 weeks
|
|
Objective Response Rate (ORR)
時間枠：24 weeks
|
ORR is defined as the proportion of participants with a complete or partial response.
|
24 weeks
|
|
Complete cell cycle arrest (CCCA)
時間枠：6 weeks
|
Ki67≤2.7%
|
6 weeks
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 2026-0359
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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