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

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: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab (Herceptin); Drug: Pertuzumab; Drug: Combination product: Trastuzumab + Pertuzumab; Drug: Docetaxel or Nab-paclitaxel; Drug: carboplatin; Drug: ADC; Drug: CDK4/6 inhibitor; Drug: Aromatase Inhibitor (AI)

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: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xu Liang; Phone Number: 010-8819 6406; Email: liangxu15@outlook.com

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
rate of pathologic complete response (pCR)	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

Outcome Measure	Measure Description	Time Frame
SUVmax change on HER2-PET	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

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; 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; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; Trastuzumab; Carboplatin; Aromatase Inhibitors; pertuzumab; 130-nm albumin-bound paclitaxel
• Other Study ID 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