Maintenance Therapy in HER2-Positive Unresectable Locally Recurrent or Metastatic Breast Cancer: A Phase II Study

NCT ID: NCT07179939

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 288 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-10
• Study Completion Date: 2031-12-30

Brief Summary

This is a phase II trial exploring the maintenance therapy with trastuzumab combined with pyrotinib or dalpiciclib and endocrine therapy in HER2-positive advanced breast cancer based on different hormone receptor (HR) statuses following trastuzumab rezetecan (T-DXh, SHR-A1811) as induction treatment for HER2-positive unresectable locally recurrent or metastatic breast cancer (MBC) patients.

Conditions

HER2-positive Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

All patients will receive a 6-cycle induction phase with T-DXh 4.8 mg/kg body weight administered as an intravenous (IV) infusion on day 1 (D1) of each 21-day cycle (Q3W).

Participants may continue with maintenance treatment if T-DXh is discontinued prematurely due to unacceptable toxicity prior to disease progression.

During the maintenance phase, participants with HR positive disease will receive trastuzumab combined with dalpiciclib and endocrine therapy and for those with HR negative disease will receive trastuzumab combined with pyrotinib.

Group Type: EXPERIMENTAL

Trastuzumab rezetecan

Intervention Type: DRUG

Trastuzumab rezetecan is a lyophilized powder for injection intravenously. Administered according to label.

Pyrotinib

Intervention Type: DRUG

320 mg/d, q.d., p.o. A course of treatment need 21 days.

Dalpiciclib

Intervention Type: DRUG

125 mg/d, q.d., p.o. day 1-21, every 28 days.

Trastuzumab

Intervention Type: DRUG

Administered according to label.

ET: Letrozole/ Anastrozole/ Exemestane/ Fulvestrant/ Leuprorelin/ Goserelin.

Intervention Type: DRUG

Administered according to label.

Interventions

Trastuzumab rezetecan

Trastuzumab rezetecan is a lyophilized powder for injection intravenously. Administered according to label.

Intervention Type: DRUG

Pyrotinib

320 mg/d, q.d., p.o. A course of treatment need 21 days.

Intervention Type: DRUG

Dalpiciclib

125 mg/d, q.d., p.o. day 1-21, every 28 days.

Intervention Type: DRUG

Trastuzumab

Administered according to label.

Intervention Type: DRUG

ET: Letrozole/ Anastrozole/ Exemestane/ Fulvestrant/ Leuprorelin/ Goserelin.

Administered according to label.

Intervention Type: DRUG

Other Intervention Names

SHR-A1811; T-DXh

Eligibility Criteria

Inclusion Criteria

To be eligible to participate in this trial, an individual must meet ALL the following criteria:

1. Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.

2. Female patients ≥ 18 years of age at the time of signing ICF.

3. Breast Cancer Requirements:

1. Histologically or cytologically confirmed HER2-positive(IHC 3+ or ISH+) unresectable locally advanced or metastatic breast cancer (Note: Patients eligible for curative-intent treatment are excluded).

2. Documented hormone receptor (HR) status.

3. No prior systemic anti-tumor therapy for recurrent/metastatic disease (≤1 line of endocrine therapy is permitted*).

4. For patients who received (neo)adjuvant therapy: >12 months between the end of systemic treatment (excluding endocrine therapy) and recurrence/metastasis.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

5. Adequate Organ Function.

6. Pregnancy and Contraception: Women of childbearing potential (WOCBP) must agree to use highly effective contraception from screening until7 months after the last dose of study treatment and must refrain from breastfeeding.

Exclusion Criteria

An individual who meets ANY of the following criteria will be excluded from participation in this trial:

1. Known active CNS metastases not treated with surgery or radiotherapy, except for those who have achieved stable disease for ≥1 month after treatment and have discontinued corticosteroids for >2 weeks.

2. Received major cancer-related surgery, radiotherapy, chemotherapy, immunotherapy, molecular targeted therapy, biologic therapy, or investigational drug therapy within 4 weeks prior to the first dose of study treatment.

3. Previous treatment with antibody-drug conjugates containing exatecan derivative topoisomerase I inhibitors.

4. Presence of clinically significant cardiovascular conditions, including:

1. Severe/unstable angina

2. Symptomatic congestive heart failure (NYHA class ≥II)

3. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention

4. Myocardial infarction within 6 months before the first dose

5. Has a history of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.

6. Known substance abuse or any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Chinese PLA General Hospital

OTHER

Sponsor Role: collaborator

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Zhimin Shao

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fudan University

Shanghai, , China

Countries

China

Other Identifiers

MA-BC-II-111

Identifier Type: -

Identifier Source: org_study_id