Breast NeoplasmsPhase 4NCT07162259
Cohort Study on Sequential ADC Therapy in HR-positive/HER2-negative Advanced Breast Cancer
A Phase 4 study testing First-line T-DXd followed by SG upon disease progression and First-line SG followed by T-DXd upon progression in people with Breast Neoplasms, run by Yan Xue at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- First-line T-DXd followed by SG upon disease progression and First-line SG followed by T-DXd upon progression
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2025to 31 Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Xi'an International Medical Center Hospital
Xi'an
Yan Xue, 0086-13992830596, 1410605462@qq.com
About this study
Official title: Real-world Cohort Study on Sequential Therapy With ADC Drugs Following Progression of Endocrine Therapy Guided by Molecular Biomarkers in HR-positive/HER2-negative Advanced Breast Cancer
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
- Being tested
- First-line T-DXd followed by SG upon disease progression, First-line SG followed by T-DXd upon progression
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
First-line T-DXd followed by SG upon disease progressionDrug
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.
First-line SG followed by T-DXd upon progressionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: First-line SG followed by T-DXd upon progression |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
PFS2 is defined as the time from the initiation of the second ADC therapy (ADC2) after progression on the first ADC therapy to the date of further disease progression or death from any cause, whichever occurs first.
Measured: 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)
PFS-Total is defined as the time from signing the informed consent form to the earliest occurrence of disease progression or death from any cause, regardless of whether it occurs during the first ADC therapy (ADC1), the second ADC therapy (ADC2) following progression, or thereafter.
Measured: 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)
OS is defined as the time from randomization to death due to any cause.
Measured: From the date of randomization until the date of death from any cause, assessed up to 60 months.
Objective Response Rate（ORR）
Measured: At least 4 weeks after first documented response
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2025
- Study start1 Oct 2025 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yan Xue
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Yan Xue, Xi'an International Medical Center Hospital
- Investigators
- Yan Xue, Principal investigator, Xi'an International Medical Center Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07162259
- Sponsor's protocol ID
- IIT2025006
- Status last verified
- Sep 2025
- First submitted
- 18 Aug 2025
- Last updated
- 9 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Since the research data involves patient privacy and intellectual property protection from collaborating institutions, the original data will not be publicly shared at this time. Summarized results will be published in academic papers.
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-world Cohort Study on Sequential Therapy With ADC Drugs Following Progression of Endocrine Therapy Guided by Molecular Biomarkers in HR-positive/HER2-negative Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT07162259
- Acronym / sponsor ID
- IIT2025006
- Conditions
- Breast Neoplasms
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Yan XueUniversity, hospital or other
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 9 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (HER2 IHC 2+) | Experimental | Drug: First-line T-DXd followed by SG upon disease progressionPatients 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. |
| Cohort 2 (HER2 IHC ≤1+) | Experimental | Drug: First-line SG followed by T-DXd upon progressionPatients 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (9 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| First-line T-DXd followed by SG upon disease progressionPatients 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. | Drug | Cohort 1 (HER2 IHC 2+) |
| First-line SG followed by T-DXd upon progressionPatients 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 | Cohort 2 (HER2 IHC ≤1+) |
Primary outcome
Progression-Free Survival (PFS1)
Time frame: 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.
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.
4 secondary outcomes
Progression-Free Survival 2 (PFS2)
Time frame: 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)
Time frame: 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)
Time frame: From the date of randomization until the date of death from any cause, assessed up to 60 months.
Objective Response Rate（ORR）
Time frame: At least 4 weeks after first documented response
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2025.
- Individual participant dataSharing planned: No. Since the research data involves patient privacy and intellectual property protection from collaborating institutions, the original data will not be publicly shared at this time. Summarized results will be published in academic papers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yan Xue principal investigator
Xi'an International Medical Center Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing First-line T-DXd followed by SG upon disease progression and First-line SG followed by T-DXd upon progression in people with Breast Neoplasms, run by Yan Xue at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Junmei Zhang (008618092309080, zjm19870908@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS1) (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2025.