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

Not Applicable

Not yet recruiting

• Conditions: HER2-positive Breast Cancer
• Interventions: Drug: Trastuzumab rezetecan; Drug: Pyrotinib; Drug: Dalpiciclib; Drug: Trastuzumab

• Registration Number: NCT07179939
• Lead Sponsor: Fudan University

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-06
• Study Start: 2025-09-10
• Study First Submitted QC: 2025-09-11
• Last Update Submitted: 2025-09-11
• Study First Posted: 2025-09-18
• Last Update Posted: 2025-09-18
• Primary Completion: 2030-12-30
• Study Completion: 2031-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 288

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	Trastuzumab rezetecan	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.
Experimental	Pyrotinib	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.
Experimental	Dalpiciclib	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.
Experimental	Trastuzumab	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.

Primary Outcome Measures

Name	Time	Method
PFS	From the date of treatment initiation until to the first occurrence of disease progression as determined locally by the investigator assessment using RECIST v.1.1 or death from any cause, whichever occurs first，assessed up to 60 months	Defined as the period from treatment initiation until to the first occurrence of disease progression as determined locally by the investigator assessment using RECIST v.1.1 or death from any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
OS	From the date of treatment initiation to the death from any cause, assessed up to 84 months	Defined as the period from treatment initiation to death from any cause, as determined locally by the investigator.
Objective response rate (ORR)	At least 4 weeks after first documented response	Defined as the rate of patients with complete response (CR) or partial response (PR), as determined locally by the investigator using RECIST v.1.1.
Safety and tolerability	From the date of treatment initiation until to the discontinuation of treatment，assessed up to 60 months	Assessed in all patients as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

Trial Locations

Locations (1)

Fudan University; 🇨🇳 Shanghai, China