ADC Based Therapy Accroding to HER2 Heterogeneous

NCT07844018 | Not Yet Recruiting Phase 2

• 1 other identifier: 2026PHB659
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

This study adopts a single-center, open-label, single-arm interventional design. It will enroll 88 patients with histologically confirmed HER2-positive early breast cancer who are suitable for surgery and neoadjuvant therapy, and stratify them by HER2 homogeneity/heterogeneity based on histological analysis. Subjects are not randomized and all will enter the intervention arm; patients with different HER2 homogeneity/heterogeneity will receive regimens based on anti-HER2 antibody-drug conjugates (ADCs). Recruitment is planned to commence in January 2027 and complete enrollment by December 2028. After obtaining fully informed consent and meeting eligibility criteria, eligible subjects will enter the trial phase and receive a regimen based on anti-HER2 ADCs. Once enrolled, subjects must receive the investigational drug within 72 hours. Each treatment cycle lasts 3 weeks, for a total of 8 cycles, and treatment will continue until the end of the course or until disease progression, unacceptable toxicity, death, withdrawal of informed consent, loss to follow-up, study completion, or study termination.

Conditions

Breast Cancer (Early Breast Cancer)

Keywords

HER2 positive; ADCs; neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• pathology complete response rate

  After completing neoadjuvant therapy, histopathological evaluation of hematoxylin and eosin (H\&E)-stained samples from the resected breast cancer tissue and all ipsilateral lymph node specimens shows no residual invasive carcinoma.

  From enrollment to the end of treatment at 6 months

Secondary Outcomes (3)

• bpCR

  From enrollment to the end of treatment at 6 months

• ORR

  From enrollment to the end of treatment at 6 months

• RCB

  From enrollment to the end of treatment at 6 months

Study Arms (1)

HER2-expression-based ADC therapy

EXPERIMENTAL

Based on HER2 immunohistochemistry (IHC) results, HER2 homogeneity/heterogeneity will be defined. Patients with homogeneous HER2 expression will receive 8 cycles of T-DXd therapy, while patients with heterogeneous HER2 expression will receive sequential T-DXd followed by THP therapy.

Drug: HER2 target therapy

Interventions

HER2 target therapy DRUG

Based on HER2 immunohistochemistry (IHC) results, HER2 homogeneity/heterogeneity will be defined. Patients with homogeneous HER2 expression will receive 8 cycles of T-DXd therapy, while patients with heterogeneous HER2 expression will receive sequential T-DXd followed by THP therapy.

HER2-expression-based ADC therapy

Eligibility Criteria

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

You may qualify if:

• years or older and be treatment-naïve breast cancer patients 2.histology confirmed invasive breast carcinoma.HER2-positive defined by our pathology department, defined as IHC 3+ or IHC 2+ with fluorescence/chromogenic in situ hybridization (FISH/CISH) confirming HER2 gene amplification; 3.Clinically staged as Stage II or III according to AJCC 8th edition 4.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 5.Adequate function of major organs to meet study safety and tolerability requirements 6.Agree to provide tissue biopsies and/or blood samples at specified study timepoints (baseline, after cycle 4, after cycle 8, and at surgical resection) for translational research purposes 7.No contraindication to breast-enhanced MRI (no contraindications to breast MRI enhancement 8.Reproductive-age women must have a negative serum pregnancy test within 7 days prior to enrollment and agree to use an effective form of contraception recognized clinically during the study and for 3 months after the last study drug administration 9.agrees to participate in this study and signs the informed consent form

You may not qualify if:

• bilateral breast cancer or presenting as recurrent or metastatic disease 2.Within the preceding 5 years prior to written informed consent, any history of malignant neoplasm other than treated cervical in situ carcinoma, skin basal cell carcinoma, or skin squamous cell carcinoma will exclude the subject 3.Within 4 weeks prior to enrollment, subjects who have undergone major surgery unrelated to breast cancer, or who have not fully recovered from such surgery, are excluded; procedures necessary for diagnostic tissue biopsy or peripheral venous catheter placement are allowed 4.History of interstitial lung disease (ILD) or non-infectious pneumonia, or current active ILD/pneumonia, or radiologic findings during screening that cannot exclude suspected ILD/pneumonia 5.Presence of significant cardiac disease or other conditions that would make participation unsafe or unsuitable 6.Severe infection within 4 weeks prior to the first dose 7.Known HIV infection or known acquired immunodeficiency syndrome (AIDS); active hepatitis B (HBV-DNA ≥ 500 IU/mL) or hepatitis C (HCV-RNA above the assay's lower limit) or co-infection with HBV and HCV; autoimmune hepatitis 8.Known hypersensitivity to the study drug or any of its excipients 9.Pregnant or lactating women; women of childbearing potential with a positive baseline pregnancy test; or women unwilling to use an effective contraception method throughout the study 10.History of definite neurologic or psychiatric disorders including epilepsy or dementia, or known history of psychiatric drug abuse, alcoholism, or substance misuse 11.Any other condition that, in the opinion of the investigator, would make participation unsuitable for this study.

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

yuan peng

CONTACT

86+13671287670; 13671287670@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: September 28, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)