Optimization of Dynamic Neoadjuvant Therapy Strategies for HER2-Positive Breast Cancer Based on HER2-PET/CT Molecular Imaging

April 14, 2026 updated by: xuliang, Peking University Cancer Hospital & Institute

A Prospective, Double-Arm Study on the Optimization of Dynamic Neoadjuvant Therapy Strategies for HER2-Positive Breast Cancer Based on HER2-PET/CT Molecular Imaging

This study evaluates HER2-PET/CT-guided dynamic optimization of neoadjuvant therapy in patients with early-stage HER2-positive breast cancer. Based on metabolic response after two cycles, patients receive either intenstified treatment (Arm A) or de-escalation treatment (Arm B), alongside with a concurrent standard-treatment control group (Arm C). The study aims to establish a response-adaptive, imaging-guided treatment paradigm to optimize neoadjuvant therapy in HER2-positive breast cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a prospective, two-arm, interventional study. Eligible patients with early-stage HER2-positive breast cancer are enrolled into Arm A (TCbHP: trastuzumab, pertuzumab, docetaxel/nab-paclitaxel, and carboplatin) or Arm B (trastuzumab, pertuzumab, CDK4/6 inhibitor, and aromatase inhibitor), based on molecular subtype and patient preference. Patients in the control group (ArmC) will receive standard TCbHP therapy without intervention. All patients will undergo HER2-PET/CT imaging at baseline and after two cycles of treatment. Metabolic response, defined as a ≥40% reduction in SUVmax of target lesions, guides subsequent therapy: responders continue the initial regimen, while non-responders switch to an alternative strategy (ADC in Arm A or TCbHP in Arm B). The primary endpoint is the total pathological complete response (tpCR) rate in Arm A and ArmB.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
156

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Voluntary participation with written informed consent obtained prior to any study-related procedures
  • Age ≥ 18 years, male or female.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  • Histologically confirmed HER2-positive (IHC 3+, or IHC 2+ with ISH amplification) stage I-III (cT1-3/cN0-2) breast cancer
  • Tumor diameter ≥ 1.5 cm assessed by imaging, with at least one PET-evaluable lesion present
  • Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status. For Arm B, ER expression ≥ 10% and must be strongly positive.
  • Adequate bone marrow, liver, and renal function: WBC > 3.0 × 10⁹/L, ANC ≥ 1.5 × 10⁹/L, PLT ≥ 100 × 10⁹/L, Hb ≥ 10.0 g/dL; total bilirubin ≤ ULN (excluding Gilbert's syndrome), ALP ≤ 2.5 × ULN, AST/ALT ≤ 1.5 × ULN; creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min.
  • Patients who participate in the trial have good compliance and are willing to comply with the follow-up visit.

Exclusion Criteria:

  • Prior treatment with any chemotherapy, anti-HER2 therapy, radiotherapy, or endocrine therapy, etc
  • Locally advanced (cT4/cN3) or bilateral breast cancer
  • Patients with known allergies to any active ingredients or excipients of investigational medicinal product
  • Other malignancy diagnosed within 5 years prior to enrollment, excluding cervical carcinoma in situ and cured melanoma skin cancer
  • Left ventricular ejection fraction (LVEF) < 55%
  • Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg)
  • Severely cardiovascular disease
  • Current known infection with HIV, hepatitis B virus, or hepatitis C virus
  • Patients with pulmonary disease requiring continuous oxygen therapy, previous history of bleeding diathesis or patient is currently receiving anti-coagulant therapy, or immunosuppressive agent
  • Major surgical procedure or significant traumatic injury
  • Patient has other concurrent severe and/or uncontrolled medical conditions.
  • Concurrent participation in other interventional clinical trial
  • History of receiving any investigational treatment within 28 days prior to randomization
  • Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol
  • Inability to lie flat or presence of psychiatric disorders such as claustrophobia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort A
The initial treatment regimen is the TCbHP (Trastuzumab + Pertuzumab + Docetaxel/Nab-paclitaxel + Carboplatin). After two cycles, patients assessed as metabolic responders by HER2 PET continue the TCbHP regimen for a total of six cycles, followed by surgery. Metabolic non-responders are switched to either SHR-A1811 (4.8 mg intravenously every 21 days) or Trastuzumab Deruxtecan (T-DXd, 5.4 mg/kg intravenously every 21 days) for four cycles of intensified therapy.
Drug: Trastuzumab (Herceptin)
8 mg/kg first dose, followed 6 mg/kg given into the vein (IV; intravenously) every 21 days
Drug: Pertuzumab
840 mg first dose, followed 420 mg given by IV every 21 days
Drug: Combination product: Trastuzumab + Pertuzumab
600 mg Pertuzumab, 600 mg Trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days
Drug: Docetaxel or Nab-paclitaxel
Docetaxe 75mg/m²/ Nab-paclitaxel：260mg/m²
Drug: carboplatin
AUC6
Drug: ADC
T-Dxd: 5.4mg/kg given into the vein (IV; intravenously) every 21 days SHR-A1811: 4.8mg/kg given into the vein (IV; intravenously) every 21 days
Experimental: Cohort B
The initial treatment regimen consists of trastuzumab + pertuzumab + CDK4/6 inhibitor + aromatase inhibitor (AI) ± GnRHa. After two cycles, patients assessed as metabolic responders by HER2 PET continue the original regimen for a total of six cycles of dual HER2-antibody (HP), followed by surgery. Non-responders are switched to the TCbHP regimen for another six cycles, followed by surgery.
Drug: Trastuzumab (Herceptin)
8 mg/kg first dose, followed 6 mg/kg given into the vein (IV; intravenously) every 21 days
Drug: Pertuzumab
840 mg first dose, followed 420 mg given by IV every 21 days
Drug: Combination product: Trastuzumab + Pertuzumab
600 mg Pertuzumab, 600 mg Trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days
Drug: Docetaxel or Nab-paclitaxel
Docetaxe 75mg/m²/ Nab-paclitaxel：260mg/m²
Drug: carboplatin
AUC6
Drug: CDK4/6 inhibitor
Ribociclib 600mg once daily every 21days/ Dalpiciclib 150mg once daily every 21days/ Palbociclib 125mg once daily every 21days
Drug: Aromatase Inhibitor (AI)
Letrozole 2.5mg once daily/ Anastrozole 1mg once daily/ Exemestane25mg once daily
Active Comparator: Cohort C
Patients who will receive surgery after completion of standard TCbHP regimen were be consecutively enrolled. Neither HER2-PET evaluation nor regimen adjustment based on the evaluation results was allowed.
Drug: Trastuzumab (Herceptin)
8 mg/kg first dose, followed 6 mg/kg given into the vein (IV; intravenously) every 21 days
Drug: Pertuzumab
840 mg first dose, followed 420 mg given by IV every 21 days
Drug: Combination product: Trastuzumab + Pertuzumab
600 mg Pertuzumab, 600 mg Trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days
Drug: Docetaxel or Nab-paclitaxel
Docetaxe 75mg/m²/ Nab-paclitaxel：260mg/m²
Drug: carboplatin
AUC6

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
rate of pathologic complete response (pCR)
Time Frame: Up to 6 months after treatment start
Proportion of participants who have no evidence by H&E staining of residual invasive disease
Up to 6 months after treatment start

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
SUVmax change on HER2-PET
Time Frame: Up to 6 months after treatment start
The change in SUVmax value of HER2-PET after 2 cycles of treatment compared to the baseline level
Up to 6 months after treatment start

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking University Cancer Hospital & Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 14, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • L259061

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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