Clinical trial · Interventional

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

NCT07589699CI-TRIAL-00111749not yet recruitingPhase 4ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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

Conditions (4)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Breast Cancer	Malignant Breast Neoplasm	CURATED_EXACT	0.92
Early-stage Breast Cancer	Early Stage Breast Carcinoma	ALIAS	0.90
HER2-positive Breast Cancer	HER2-Positive Breast Carcinoma	ALIAS	0.90
Locally Advanced Breast Cancer	Malignant Breast Neoplasm	CURATED_BROADER	0.78

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
Trastuzumab Rezetecan	Drug	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Experimental: Trastuzumab Rezetecan (T-DXh) as Continued Neoadjuvant Therapy
description
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).
interventionNames
1. Drug: Trastuzumab Rezetecan

Primary outcomes (1)

measure
Total Pathological Complete Response (tpCR)
timeFrame
At the time of surgery, approximately 12 weeks after the start of the 4-cycle Trastuzumab Rezetecan treatment.
description
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.

Secondary outcomes (4)

Eligibility

Eligibility (as posted)

Sex: Female
Minimum age: 18 Years

Show eligibility criteria text

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.

References

Publications (0)

Data not yet available

No reference posted for this study.