Fovinaciclib Plus Aromatase Inhibitors and Dual HER2 Blockade in a Response-Adapted Neoadjuvant Strategy for HR-Positive/HER2-Positive Early Breast Cancer

NCT07616427 | Recruiting Phase 2

• 1 other identifier: 2026-0359
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

HR+/HER2+ Early Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Breast Pathological Complete Response (bpCR) Rate: ypT0/Tis

  24 weeks

• Objective Response Rate (ORR)

  24 weeks

• Event-Free Survival (EFS)

  Approximately five years

• Adverse Event (AE)

  Approximately three years

• Complete cell cycle arrest (CCCA)

  6 weeks

Study Arms (1)

Culmerciclib + AI +HP

EXPERIMENTAL

fovinaciclib in combination with aromatase inhibitors and dual HER2 blockade

Drug: Fovinaciclib; Drug: Aromatase Inhibitors; Drug: Trastuzumab + Pertuzumab

Interventions

Fovinaciclib DRUG

CDK4/6 inhibitor

Culmerciclib + AI +HP

Aromatase Inhibitors DRUG

Letrozole or anastrozole

Culmerciclib + AI +HP

Trastuzumab + Pertuzumab DRUG

dual HER2 blockade

Culmerciclib + AI +HP

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (3)

The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

2nd Affiliated Hospital, School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

Ningbo No. 2 Hospital

Ningbo, Zhejiang, 315010, China

RECRUITING

MeSH Terms

Interventions

Aromatase Inhibitors; Trastuzumab; pertuzumab

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yunxiang Zhou

CONTACT

15868131018; yxzhou@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2026
• First Posted: June 1, 2026
• Study Start: May 20, 2026
• Primary Completion (Estimated): May 20, 2028
• Study Completion (Estimated): May 20, 2033
• Last Updated: June 1, 2026

Record last verified: 2026-05

Locations

CN (3)