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

NCT07179939 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: MA-BC-II-111
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• PFS

  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.

  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

Secondary Outcomes (3)

• OS

  From the date of treatment initiation to the death from any cause, assessed up to 84 months

• Objective response rate (ORR)

  At least 4 weeks after first documented response

• Safety and tolerability

  From the date of treatment initiation until to the discontinuation of treatment，assessed up to 60 months

Study Arms (1)

Experimental

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.

Drug: Trastuzumab rezetecan; Drug: Pyrotinib; Drug: Dalpiciclib; Drug: Trastuzumab; Drug: ET: Letrozole/ Anastrozole/ Exemestane/ Fulvestrant/ Leuprorelin/ Goserelin.

Interventions

Trastuzumab rezetecan DRUG

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

Also known as: SHR-A1811, T-DXh

Experimental

Pyrotinib DRUG

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

Experimental

Dalpiciclib DRUG

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

Experimental

Trastuzumab DRUG

Administered according to label.

Experimental

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

Administered according to label.

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this trial, an individual must meet ALL the following criteria:
• 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.
• Female patients ≥ 18 years of age at the time of signing ICF.
• Breast Cancer Requirements:
• 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).
• Documented hormone receptor (HR) status.
• No prior systemic anti-tumor therapy for recurrent/metastatic disease (≤1 line of endocrine therapy is permitted\*).
• For patients who received (neo)adjuvant therapy: \>12 months between the end of systemic treatment (excluding endocrine therapy) and recurrence/metastasis.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Adequate Organ Function.
• 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.

You may not qualify if:

• An individual who meets ANY of the following criteria will be excluded from participation in this trial:
• 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.
• 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.
• Previous treatment with antibody-drug conjugates containing exatecan derivative topoisomerase I inhibitors.
• Presence of clinically significant cardiovascular conditions, including:
• Severe/unstable angina
• Symptomatic congestive heart failure (NYHA class ≥II)
• Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention
• Myocardial infarction within 6 months before the first dose
• 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.
• Known substance abuse or any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation.

Sponsors & Collaborators

• Fudan University: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator
• Chinese PLA General Hospital: collaborator

Study Sites (1)

Fudan University

Shanghai, China

Location

MeSH Terms

Interventions

pyrotinib; dalpiciclib; Trastuzumab; Anastrozole; exemestane; Fulvestrant; Leuprolide; Goserelin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 6, 2025
• First Posted: September 18, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2031
• Last Updated: September 18, 2025

Record last verified: 2025-08

Locations

CN (1)