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

NCT07527806 | Not Yet Recruiting Phase 2

• 1 other identifier: L259061
• Study Type: interventional
• Target: 156
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Breast Cancer

Keywords

breast cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• SUVmax change on HER2-PET

  Up to 6 months after treatment start

Study Arms (3)

Cohort A

EXPERIMENTAL

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); Drug: Pertuzumab; Drug: Combination product: Trastuzumab + Pertuzumab; Drug: Docetaxel or Nab-paclitaxel; Drug: carboplatin; Drug: ADC

Cohort B

EXPERIMENTAL

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); Drug: Pertuzumab; Drug: Combination product: Trastuzumab + Pertuzumab; Drug: Docetaxel or Nab-paclitaxel; Drug: carboplatin; Drug: CDK4/6 inhibitor; Drug: Aromatase Inhibitor (AI)

Cohort C

ACTIVE COMPARATOR

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); Drug: Pertuzumab; Drug: Combination product: Trastuzumab + Pertuzumab; Drug: Docetaxel or Nab-paclitaxel; Drug: carboplatin

Interventions

Trastuzumab (Herceptin) DRUG

8 mg/kg first dose, followed 6 mg/kg given into the vein (IV; intravenously) every 21 days

Cohort A; Cohort B; Cohort C

Pertuzumab DRUG

840 mg first dose, followed 420 mg given by IV every 21 days

Cohort A; Cohort B; Cohort C

Combination product: Trastuzumab + Pertuzumab DRUG

600 mg Pertuzumab, 600 mg Trastuzumab, and 20,000 units hyaluronidase will be given by subcutaneous injection every 21 days

Cohort A; Cohort B; Cohort C

Docetaxel or Nab-paclitaxel DRUG

Docetaxe 75mg/m²/ Nab-paclitaxel：260mg/m²

Cohort A; Cohort B; Cohort C

carboplatin DRUG

AUC6

Cohort A; Cohort B; Cohort C

CDK4/6 inhibitor DRUG

Ribociclib 600mg once daily every 21days/ Dalpiciclib 150mg once daily every 21days/ Palbociclib 125mg once daily every 21days

Cohort B

Aromatase Inhibitor (AI) DRUG

Letrozole 2.5mg once daily/ Anastrozole 1mg once daily/ Exemestane25mg once daily

Cohort B

ADC DRUG

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

Cohort A

Eligibility Criteria

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

You may qualify if:

• Voluntary participation with written informed consent obtained prior to any 2.Age ≥ 18 years, male or female. 3.Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 4.Histologically confirmed HER2-positive (IHC 3+, or IHC 2+ with ISH amplification) stage I-III (cT1-3/cN0-2) breast cancer 5.Tumor diameter ≥ 1.5 cm assessed by imaging, with at least one PET-evaluable lesion presenst 6.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.

You may not qualify if:

• Prior treatment with any chemotherapy, anti-HER2 therapy, radiotherapy, or endocrine therapy, etc.
• Locally advanced (cT4/cN3) or bilateral breast cancer. 3.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; 5.Left ventricular ejection fraction (LVEF) \< 55% 6.Uuncontrolled hypertension (systolic \> 150 mm Hg and/or diastolic \> 100 mm Hg) 7.Severely cardiovascular disease 8.Current known infection with HIV, hepatitis B virus, or hepatitis C virus 9.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. 11.Patient has other concurrent severe and/or uncontrolled medical conditions. 12.Concurrent participation in other interventional clinical trial. 13.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.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab; Docetaxel; 130-nm albumin-bound paclitaxel; Carboplatin; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; 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

Central Study Contacts

Xu Liang

CONTACT

010-8819 6406; liangxu15@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 14, 2026
• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 14, 2026

Record last verified: 2026-04