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

A Single-Arm, Exploratory Study of 4 Additional Cycles of Trastuzumab Rezetecan (T-DXh) as Neoadjuvant Therapy in Patients With Early or Locally Advanced HER2-Positive Breast Cancer Who Have Non-pCR After TCbHP Neoadjuvant Therapy

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; HER2-positive Breast Cancer; Locally Advanced Breast Cancer; Early-stage Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab Rezetecan

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xiaoan Liu; Phone Number: 86-25-83714511; Email: liuxiaoan@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Any other condition assessed by the investigator as unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: Trastuzumab Rezetecan (T-DXh) as Continued Neoadjuvant Therapy; 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; 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.; Other Names: SHR-A1811; T-DXh

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-Free Survival (EFS)	Time from first dose of study treatment to the earliest occurrence of any of the following: disease progression (per RECIST 1.1), local/regional/distant recurrence, second primary tumor (breast or other), or death from any cause.	From first dose up to 5 years after last patient enrolled.
Overall Survival (OS)	Time from first dose of study treatment to death from any cause.	From first dose up to 5 years after last patient enrolled.
3-Year Invasive Disease-Free Survival (iDFS) Rate	Percentage of patients who are free from invasive disease at 3 years after surgery. Invasive disease events include ipsilateral invasive breast tumor recurrence, local/regional invasive recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, or death from any cause.	3 years after surgery.
Incidence of Adverse Events (AEs)	Number of participants experiencing adverse events. AEs are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0.	From signing of informed consent until 28 days after the last dose of study treatment.

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 26-OBU-JS-BC-II-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share individual participant data (IPD) at this time. Only aggregated results will be reported in publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No