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)

This prospective, response-adapted phase II study evaluates the efficacy and safety of neoadjuvant fovinaciclib in combination with aromatase inhibitors and dual HER2 blockade in patients with HR-positive/HER2-positive early breast cancer. All patients initially receive induction treatment with fovinaciclib plus endocrine therapy and HER2-targeted therapy, followed by early assessment of treatment response after 6 weeks of treatment. Patients demonstrating an adequate response continue the same regimen, whereas those with a suboptimal response are transitioned to standard neoadjuvant chemotherapy combined with HER2-targeted therapy prior to surgery. This adaptive approach aims to optimize treatment selection, improve therapeutic efficacy, and reduce unnecessary chemotherapy exposure.

Study Overview

• Status: Recruiting
• Conditions: HR+/HER2+ Early Breast Cancer
• Intervention / Treatment: Drug: Aromatase Inhibitors; Drug: Fovinaciclib; Drug: Trastuzumab + Pertuzumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yunxiang Zhou; Phone Number: 15868131018; Email: yxzhou@zju.edu.cn

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital of Nanjing Medical University
      • Contact: Xiaoan Liu; Phone Number: 025-83718836; Email: liuxiaoan@126.com
      • Principal Investigator: Xiaoan Liu
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine
      • Principal Investigator: Yiding Chen
      • Contact: Yunxiang Zhou; Phone Number: 15868131018; Email: ydchen@zju.edu.cn
      • Contact: Email: ydchen@zju.edu.cn
    • Ningbo, Zhejiang, China, 315010
      • Recruiting
      • Ningbo No. 2 Hospital
      • Principal Investigator: Xujun Li
      • Contact: Wei Zhang; Phone Number: 13586562390; Email: 20949061@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Culmerciclib + AI +HP; fovinaciclib in combination with aromatase inhibitors and dual HER2 blockade	Drug: Aromatase Inhibitors; Letrozole or anastrozole; Drug: Fovinaciclib; CDK4/6 inhibitor; Drug: Trastuzumab + Pertuzumab; dual HER2 blockade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Pathological Complete Response (tpCR) Rate: ypT0/Tis, ypN0	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-Free Survival (EFS)	EFS is defined as the time from randomization to any of the following events: precludes surgery, local or distant recurrence, second primary malignancy, or death due to any cause.	Approximately five years
Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a study participant administered a medicinal product, temporally associated with study intervention, without presumption of causality.	Approximately three years
Breast Pathological Complete Response (bpCR) Rate: ypT0/Tis	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)	ORR is defined as the proportion of participants with a complete or partial response.	24 weeks
Complete cell cycle arrest (CCCA)	Ki67≤2.7%	6 weeks

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2026
• Primary Completion (Estimated): May 20, 2028
• Study Completion (Estimated): May 20, 2033

Study Registration Dates

• First Submitted: May 24, 2026
• First Submitted That Met QC Criteria: May 24, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Amino Acids, Peptides, and Proteins; Proteins; Pharmacologic Actions; Chemical Actions and Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Trastuzumab; Aromatase Inhibitors; pertuzumab
• Other Study ID Numbers: 2026-0359

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No