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)
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Yunxiang Zhou
- Número de teléfono: 15868131018
- Correo electrónico: yxzhou@zju.edu.cn
Ubicaciones de estudio
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Jiangsu
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Nanjing, Jiangsu, Porcelana, 210029
- Reclutamiento
- The First Affiliated Hospital of Nanjing Medical University
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Contacto:
- Xiaoan Liu
- Número de teléfono: 025-83718836
- Correo electrónico: liuxiaoan@126.com
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Investigador principal:
- Xiaoan Liu
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Zhejiang
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Hangzhou, Zhejiang, Porcelana, 310009
- Reclutamiento
- 2nd Affiliated Hospital, School of Medicine
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Investigador principal:
- Yiding Chen
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Contacto:
- Yunxiang Zhou
- Número de teléfono: 15868131018
- Correo electrónico: ydchen@zju.edu.cn
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Contacto:
- Correo electrónico: ydchen@zju.edu.cn
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Ningbo, Zhejiang, Porcelana, 315010
- Reclutamiento
- Ningbo No. 2 Hospital
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Investigador principal:
- Xujun Li
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Contacto:
- Wei Zhang
- Número de teléfono: 13586562390
- Correo electrónico: 20949061@qq.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Culmerciclib + AI +HP
fovinaciclib in combination with aromatase inhibitors and dual HER2 blockade
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Letrozole or anastrozole
CDK4/6 inhibitor
dual HER2 blockade
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Total Pathological Complete Response (tpCR) Rate: ypT0/Tis, ypN0
Periodo de tiempo: 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.
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24 weeks
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Supervivencia sin eventos (EFS)
Periodo de tiempo: Aproximadamente cinco años
|
EFS se define como el tiempo desde la aleatorización hasta cualquiera de los siguientes eventos: impide la cirugía, la recurrencia local o distante, la segunda malignidad primaria o la muerte debido a cualquier causa.
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Aproximadamente cinco años
|
|
Evento adverso (AE)
Periodo de tiempo: Aproximadamente tres años
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Un AE se define como cualquier ocurrencia médica desagradable en un participante de un estudio que administró un medicamento, asociado temporalmente con la intervención del estudio, sin presunción de causalidad.
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Aproximadamente tres años
|
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Breast Pathological Complete Response (bpCR) Rate: ypT0/Tis
Periodo de tiempo: 24 weeks
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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).
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24 weeks
|
|
Objective Response Rate (ORR)
Periodo de tiempo: 24 weeks
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ORR is defined as the proportion of participants with a complete or partial response.
|
24 weeks
|
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Complete cell cycle arrest (CCCA)
Periodo de tiempo: 6 weeks
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Ki67≤2.7%
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6 weeks
|
Colaboradores e Investigadores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica.
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Inhibidores de enzimas
- Inhibidores de la síntesis de esteroides
- Antagonistas hormonales
- Antagonistas de estrógenos
- Aminoácidos, péptidos y proteínas
- Proteínas
- Acciones farmacológicas
- Acciones y usos químicos
- Anticuerpos, monoclonales, humanizados
- Anticuerpos, monoclonal
- Anticuerpos
- Inmunoglobulinas
- Inmunoproteínas
- Proteínas de la sangre
- Globulinas séricas
- Globulinas
- Trastuzumab
- Inhibidores de la aromatasa
- pertuzumab
Otros números de identificación del estudio
- 2026-0359
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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