Trastuzumab Rezetecan vs Trastuzumab Deruxtecan in the Neoadjuvant Treatment of HER2 Positive Breast Cancer

February 10, 2026 updated by: Zhenzhen Liu, Henan Cancer Hospital

A Randomized, Open-Label, Phase II Study Comparing the Efficacy and Safety of Trastuzumab-rezetecan and Trastuzumab Deruxtecan (T-DXd) in Neoadjuvant Treatment of Patients With HER2-Positive Early or Locally Advanced Breast Cancer

This is a single-center, randomized, open-label, phase II interventional study. Eligible patients will be randomized 1:1 to receive either Trastuzumab-rezetecan (4.8 mg/kg Q3W) or T-DXd (5.4 mg/kg Q3W) for 8 neoadjuvant cycles. After completing neoadjuvant treatment, patients will undergo definitive surgery, and tpCR will be assessed from resected specimens. Patients will then be followed up to monitor long-term efficacy (e.g., EFS) and late-onset adverse events. A total of 68 patients (34 per arm) will be enrolled to achieve the study's statistical objectives.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

68

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Female, 18-75 years old, treatment-naive
  2. ECOG PS 0-1
  3. Histologically confirmed HER2+ (IHC 3+ or IHC 2+/ISH+) early/locally advanced breast cancer (AJCC 8th: cT2-cT4 any N cM0) or cT1c N+ cM0; known ER/PR status
  4. Adequate organ function (hematology/biochemistry/coagulation/urine/cardiac)
  5. Negative pregnancy test (childbearing women); agree to effective contraception
  6. Sign an informed consent form.

Exclusion Criteria:

  1. Bbilateral/inflammatory/occult breast cancer.
  2. Prior anti-tumor therapy (chemotherapy/radiotherapy/targeted therapy, etc.); radical radiotherapy (4 weeks prior) or palliative radiotherapy (2 weeks prior) to first dose.
  3. Concurrent anti-tumor therapy; other malignancies (within past 5 years, except cured basal cell carcinoma/cervical CIS).
  4. Prior trial participation (past 4 weeks); systemic immunosuppressants/hormones (>10 mg/day prednisone equivalent, 2 weeks prior; nasal/inhaled steroids excluded).
  5. Live/attenuated vaccine (past 4 weeks); major non-breast surgery (4 weeks prior, incomplete recovery).
  6. Active/relapsing autoimmune disease (except controlled hypothyroidism/well-managed skin diseases/type 1 diabetes); immunodeficiency (HIV+/organ transplant).
  7. Uncontrolled cardiovascular/cerebrovascular disease (e.g., MI/stroke in 6 months, NYHA III-IV heart failure, QTcF >470 msec [female]).
  8. Active ILD/severe lung disease; active hepatitis B (HBsAg+ & HBV DNA ≥500 IU/mL)/hepatitis C (HCV RNA+); severe infection requiring anti-infective therapy.
  9. Bleeding/thrombotic tendency; hypersensitivity to study drugs/excipients.
  10. Pregnant/lactating women; women of childbearing potential with positive pregnancy test or refusing contraception.
  11. Other conditions (e.g., uncontrolled hypertension/diabetes, neuropsychiatric disorders) deemed unsuitable by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: trastuzumab-rezetecan group
Drug: Trastuzumab rezetecan
Participants will receive Trastuzumab-rezetecan for 8 cycles
Active Comparator: trastuzumab deruxtecan group
Drug: Trastuzumab deruxtecan
Participants will receive Trastuzumab deruxtecan for 8 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pathological Complete Response Rate
Time Frame: 3 to 8 weeks after neoadjuvant treatment completion
3 to 8 weeks after neoadjuvant treatment completion

Secondary Outcome Measures

Outcome Measure
Time Frame
3-Year Event-Free Survival (EFS) Rate
Time Frame: 3 years after randomization
3 years after randomization
Objective Response Rate (ORR)
Time Frame: Within 6 months after randomization
Within 6 months after randomization
Event-Free Survival (EFS)
Time Frame: 5-10 years
5-10 years
EORTC QLQ-C30
Time Frame: Within 1 year after randomization
Within 1 year after randomization
QLQ-BR23
Time Frame: within 1 year after randomization
within 1 year after randomization
Adverse enents
Time Frame: First dose to 30 days after last dose
First dose to 30 days after last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Henan Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

July 1, 2030

Study Registration Dates

First Submitted

February 10, 2026

First Submitted That Met QC Criteria

February 10, 2026

First Posted (Actual)

February 18, 2026

Study Record Updates

Last Update Posted (Actual)

February 18, 2026

Last Update Submitted That Met QC Criteria

February 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HELEN-026 ADC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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