Efficacy and Safety of Trastuzumab-rezetecan in HER2-Expressing Breast Cancer

Efficacy and Safety of Trastuzumab-rezetecan in HER2-Positive and HER2-Low Breast Cancer: A Multicenter, Observational, Real-World Study Protocol

This study is a multicenter, observational, real-world investigation. The research plans to enroll 300 HER2-positive and HER2-low breast cancer patients who meet the inclusion criteria. All patients included in the analysis are currently receiving or are scheduled to receive a treatment regimen containing Trastuzumab-rezetecan. There are no restrictions on the treatment regimen, which is entirely based on the clinician's choice. The study aims to evaluate the efficacy and safety of the treatment regimen containing Trastuzumab-rezetecan.

After completing screening examinations and assessments, eligible patients will enter the study treatment phase. They will receive the treatment regimen containing Trastuzumab-rezetecan and undergo follow-up visits according to the protocol. During the study treatment period, patients will undergo imaging and safety assessments as per clinical routine, with the investigator's assessment serving as the final result. Upon treatment completion or study withdrawal, corresponding safety examinations and imaging assessment data will be collected. For neoadjuvant patients, pathological complete response (pCR) will be assessed post-surgery by pathologists at the participating centers.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Breast Cancer; HER2-low Breast Cancer; Trastuzumab-rezetecan
• Intervention / Treatment: Drug: Trastuzumab-rezetecan Treatment Group

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
      • Contact: Jianli Zhao; Phone Number: +86 15920589334; Email: zhaojianli1988@126.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

HER2-positive and HER2-low breast cancer patients, including all those analyzed who are currently receiving or plan to receive a treatment regimen containing Trastuzumab-rezetecan.

Description

Inclusion Criteria:

1. Age ≥ 18 years, with pathologically confirmed HER2-positive or HER2-low-expressing breast cancer: HER2-positive is defined as IHC 3+ or IHC 2+ with a positive ISH result; HER2-low-expressing is defined as IHC 1+ or IHC 2+ with a negative ISH result for HER2 amplification; hormone receptor status must be clearly documented.
2. Planned to receive treatment with Trastuzumab-rezetecan for Injection in the neoadjuvant, adjuvant, or advanced/metastatic setting; patients with advanced/metastatic disease must have progressed after at least one prior line of systemic therapy.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
4. Women of childbearing potential must have a negative serum pregnancy test within 28 days prior to enrollment, and both male and female patients must be willing to use a highly effective, medically approved method of contraception during the study and for 1 year after the last dose of the study drug.
5. Non-pregnant and non-lactating female patients.
6. Not concurrently participating in any other ongoing clinical studies. The patient or their legal representative has provided informed consent by signing the informed consent form and is willing and able to comply with scheduled visits, the study treatment plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

1. Any evidence of severe or uncontrolled systemic disease, including uncontrolled hypertension, active bleeding disorders, active infections (such as hepatitis B, hepatitis C, and human immunodeficiency virus), or severely impaired bone marrow reserve or organ function (including hepatic and renal impairment), which, in the investigator's opinion, would significantly alter the risk-benefit balance.
2. At the initiation of treatment with Trastuzumab-rezetecan for Injection, the patient has not recovered from any prior treatment-related toxicity of CTCAE grade >3.
3. Known history of hypersensitivity to Trastuzumab-rezetecan for Injection, its excipients, or drugs with similar chemical structures or classes as Trastuzumab-rezetecan.
4. Patients deemed unsuitable for enrollment by the investigator.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Trastuzumab-rezetecan Treatment Group

Drug: Trastuzumab-rezetecan Treatment Group; Trastuzumab-rezetecan: 4.8 mg/kg (for HER2-positive) or 6.4 mg/kg (for HER2-low) per treatment cycle of 21 days. The dosage is to be adjusted at the discretion of the investigator based on the actual clinical situation. All patients will receive treatment with a regimen containing Trastuzumab-rezetecan as determined by the investigator. The regimens for other concomitant medications will be selected by the treating physician based on the patient's individual circumstances.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	Assessed per NCI-CTCAE v5.0 criteria	From the signing of the informed consent form until 30 days after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response(pCR）	No residual invasive cancer is found upon evaluation of the excised breast tissue and regional lymph nodes	Estimated 7 years
Invasive disease free survival(iDFS)	Time from randomization to the first occurrence of ipsilateral local/regional invasive recurrence, distant metastasis, contralateral invasive breast cancer, or death from any cause.	Estimated 7 years
Progression-free survival (PFS)	The date of randomization to the first documented disease progression (per RECIST 1.1) or death due to any cause, whichever occurred first	Estimated 7 years
Objective Response Rate (ORR)	The percentage of patients with ≥30% tumor shrinkage, as evaluated by investigators per RECIST 1.1 criteria	Estimated 7 years
Clinical Benefit Rate (CBR)	Sum of complete response [CR], partial response [PR], and SD lasting ≥24 weeks), as assessed by investigators according to RECIST 1.1 criteria	Estimated 7 years
Overall Survival (OS)	The duration from randomization to death event	Estimated 7 years

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2031

Study Registration Dates

• First Submitted: January 14, 2026
• First Submitted That Met QC Criteria: January 14, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: SYSKY-2025-613-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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