Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer

NCT07162259 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: IIT2025006
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy is the standard first-line treatment for advanced HR+ (hormone receptor-positive)/HER2- (human epidermal growth factor receptor 2-negative) breast cancer. However, the optimal treatment strategy after CDK4/6i progression remains unclear. In recent years, antibody-drug conjugates (ADCs) such as sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have demonstrated significant activity in HR+/HER2- breast cancer, providing new options post-CDK4/6i progression. Yet, the optimal sequencing of different ADCs (e.g., SG followed by T-DXd vs. T-DXd followed by SG) after CDK4/6i failure remains uncertain. Determining how to further optimize treatment selection to prolong survival and improve quality of life has become a key research focus in clinical practice. This study aims to explore the efficacy, safety, and potential resistance mechanisms of biomarker-guided sequential ADC therapy (e.g., SG→T-DXd vs. T-DXd→SG) following CDK4/6i progression. The findings may guide clinical decision-making and provide evidence for precision medicine.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS1)

  PFS1 is defined as the time from signing the informed consent form to the first documented disease progression after initial ADC therapy or death from any cause, whichever occurs first.

  From the date of signing the informed consent form until the date of first documented disease progression after initial ADC therapy or date of death from any cause (whichever occurs first), assessed up to 24 months.

Secondary Outcomes (4)

• Progression-Free Survival 2 (PFS2)

  From the date of initiation of the second ADC therapy (ADC2) until the date of further documented disease progression or date of death from any cause (whichever occurs first), assessed up to 24 months.

• Composite Progression-Free Survival (PFS-Total)

  From the date of signing the informed consent form until the date of the first documented disease progression (during ADC1 or ADC2 therapy) or date of death from any cause (whichever occurs first), assessed up to 36 months.

• Overall Survival (OS)

  From the date of randomization until the date of death from any cause, assessed up to 60 months.

• Objective Response Rate（ORR）

  At least 4 weeks after first documented response

Study Arms (2)

Cohort 1 (HER2 IHC 2+)

EXPERIMENTAL

Patients will be assigned to Cohort 1 (HER2 Immunohistochemistry，IHC，2+) based on different HER2 immunohistochemical expression levels, where they will first receive T-DXd treatment, followed by SG treatment upon disease progression.

Drug: First-line T-DXd followed by SG upon disease progression

Cohort 2 (HER2 IHC ≤1+)

EXPERIMENTAL

Patients will be assigned to Cohort 2 (HER2 IHC ≤1+) based on different HER2 immunohistochemical expression levels, where they will first receive SG treatment, followed by T-DXd treatment upon disease progression.

Drug: First-line SG followed by T-DXd upon progression

Interventions

First-line T-DXd followed by SG upon disease progression DRUG

Patients will be assigned to Cohort 1 (HER2 IHC 2+) based on different HER2 immunohistochemical expression levels, where they will first receive T-DXd treatment, followed by SG treatment upon disease progression.

Cohort 1 (HER2 IHC 2+)

First-line SG followed by T-DXd upon progression DRUG

Patients will be assigned to Cohort 2 (HER2 IHC ≤1+) based on different HER2 immunohistochemical expression levels, where they will first receive SG treatment, followed by T-DXd treatment upon disease progression.

Cohort 2 (HER2 IHC ≤1+)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ≥18 years old;
• Histologically or cytologically confirmed HR+/HER2- (HER2 IHC 0/IHC 1+ or IHC 2+ with FISH-negative) locally advanced unresectable or metastatic breast cancer, as defined by ASCO/CAP guidelines;
• Prior treatment with CDK4/6i combined with endocrine therapy, with radiologically confirmed disease progression;
• Presence of evaluable lesions;
• Received ≤2 lines of chemotherapy for advanced disease;
• Adequate organ function and performance status (ECOG score ≤2);
• Signed informed consent.

You may not qualify if:

• Previous treatment with topoisomerase 1 (TOP-1) inhibitor-based therapy;
• Severe cardiac, hepatic, or renal dysfunction or other serious comorbidities;
• History of moderate to severe interstitial lung disease (ILD) with concurrent pulmonary insufficiency;
• Symptomatic brain metastases;
• History of allergy to key components of the investigational ADC drugs (e.g., payload, antibody, or linker);
• Patients with active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or a history of intestinal obstruction or gastrointestinal (GI) perforation;
• Uncontrolled cardiovascular diseases (e.g., NYHA Class III/IV heart failure, myocardial infarction within 6 months);
• Active infections (e.g., HIV, active HBV/HCV infection);
• Pregnant or lactating women.

Sponsors & Collaborators

• Yan Xue: lead

Study Sites (1)

Xi'an International Medical Center Hospital

Xi'an, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Yan Xue

  Xi'an International Medical Center Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junmei Zhang

CONTACT

008618092309080; zjm19870908@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the First Department of Oncology, Xi'an International Medical Center Hospital

Study Record Dates

• First Submitted: August 18, 2025
• First Posted: September 9, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)