Trastuzumab Rezetecan (T-DXh) in HER2+ Breast Cancer With Non-pCR After TCbHP

NCT07589699 | Not Yet Recruiting Phase 4

• 1 other identifier: 26-OBU-JS-BC-II-017
• Study Type: interventional
• Target: 59
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, multi-center, single-arm, phase 2 exploratory study to evaluate the efficacy and safety of adding 4 cycles of Trastuzumab Rezetecan (T-DXh), an anti-HER2 antibody-drug conjugate, as continued neoadjuvant therapy in patients with early or locally advanced HER2-positive breast cancer who have residual invasive disease after standard 6-cycle TCbHP (taxane, carboplatin, trastuzumab, pertuzumab) neoadjuvant therapy. Patients will receive 4 cycles of T-DXh (4.8 mg/kg IV Q3W) followed by radical surgery. The primary endpoint is tpCR rate. Secondary endpoints include ORR, EFS, OS, 3-year iDFS, and safety. Simon's two-stage design (H0: pCR ≤10%, H1: pCR ≥25%, α=0.05, β=0.2) requires 43 evaluable patients; with 10% dropout, 48 patients will be enrolled.

Conditions

Breast Cancer; HER2-positive Breast Cancer; Early-stage Breast Cancer; Locally Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Total Pathological Complete Response (tpCR)

  Absence of invasive residual cancer in both the breast primary tumor and axillary lymph nodes (ypT0/is, ypN0) after neoadjuvant therapy and surgery. Presence of ductal carcinoma in situ (DCIS) is allowed.

  At the time of surgery, approximately 12 weeks after the start of the 4-cycle Trastuzumab Rezetecan treatment.

Secondary Outcomes (4)

• Event-Free Survival (EFS)

  From first dose up to 5 years after last patient enrolled.

• Overall Survival (OS)

  From first dose up to 5 years after last patient enrolled.

• 3-Year Invasive Disease-Free Survival (iDFS) Rate

  3 years after surgery.

• Incidence of Adverse Events (AEs)

  From signing of informed consent until 28 days after the last dose of study treatment.

Study Arms (1)

Experimental: Trastuzumab Rezetecan (T-DXh) as Continued Neoadjuvant Therapy

EXPERIMENTAL

Patients with residual invasive disease after standard 6 cycles of TCbHP neoadjuvant therapy receive 4 cycles of Trastuzumab Rezetecan (T-DXh) 4.8 mg/kg intravenously every 3 weeks (Q3W), followed by radical surgery. After surgery: * Patients achieving pathological complete response (pCR) receive 7 additional cycles of T-DXh as adjuvant therapy. * Patients not achieving pCR receive investigator-selected adjuvant therapy (optional: trastuzumab + pertuzumab followed by 1 year of pyrotinib).

Drug: Trastuzumab Rezetecan

Interventions

Trastuzumab Rezetecan DRUG

An anti-HER2 antibody-drug conjugate (ADC) consisting of a humanized HER2-targeting monoclonal antibody (trastuzumab) conjugated to a DNA topoisomerase I inhibitor (SHR169265) via a cleavable tetrapeptide linker.

Also known as: T-DXh, SHR-A1811

Experimental: Trastuzumab Rezetecan (T-DXh) as Continued Neoadjuvant Therapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• For premenopausal and perimenopausal patients: negative pregnancy test and agreement to use reliable contraception during the treatment period.
• Pathologically confirmed HER2-positive invasive breast cancer (IHC 3+ or IHC 2+ with FISH+).
• Completed standard neoadjuvant TCbHP (taxane + carboplatin + trastuzumab + pertuzumab) with imaging assessment not achieving clinical complete remission (non-cCR).
• Agree to undergo a core needle biopsy.
• ECOG performance status 0 or 1.
• Adequate organ function meeting the following criteria: hemoglobin ≥ 90 g/L, white blood cell count ≥ 3.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, absolute neutrophil count ≥ 1.5 × 10\^9/L, AST/ALT ≤ 3 × ULN, total bilirubin ≤ 1.5 × ULN, serum creatinine ≤ 1.5 × ULN.
• No myocardial ischemia on ECG; New York Heart Association (NYHA) functional class I; left ventricular ejection fraction (LVEF) ≥ 55% by echocardiography; cardiac troponin I (cTnI) and brain natriuretic peptide (BNP) within normal limits.
• Signed informed consent.

You may not qualify if:

• Male breast cancer or inflammatory breast cancer.
• Metastatic breast cancer (Stage IV).
• Concurrent other malignancy or history of other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
• Concurrent other anti-tumor therapy or participation in another clinical trial.
• Severe non-malignant disease that would affect compliance or place the patient at risk.
• Major surgery within 4 weeks prior to start of study treatment or anticipated need for major surgery during the study.
• History of allergic reaction or contraindication to any component of the study drug.
• Dementia, mental abnormality, or any psychiatric illness that interferes with understanding of the informed consent.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Xiaoan Liu

CONTACT

86-25-83714511; liuxiaoan@126.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 11, 2026
• First Posted: May 15, 2026
• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2031
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share