Advanced Breast Cancer With Ultra-Low HER2 ExpressionPhase 2NCT07817082
Phase II Study of SHR-A1811 for Ultra-Low HER2 Advanced Breast Cancer
A Phase 2 study testing SHR- A1811 in people with Advanced Breast Cancer With Ultra-Low HER2 Expression, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
Trial summary
This is a single-center, single-arm, open-label phase II exploratory study. A total of 30 patients aged 18-75 years with ECOG PS 0-1, pathologically confirmed advanced breast cancer with ultra-low HER2 expression will be enrolled. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Advanced Breast Cancer With Ultra-Low HER2 Expression
- What is being tested?
- SHR- A1811
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2026to 31 Mar 2029
- Phase
- Phase 2
- 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 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female subjects, aged ≥18 years and ≤75 years;
- ECOG performance status 0-1;
- Expected survival of no less than 3 months;
- Histologically documented breast cancer:
- Advanced or metastatic breast cancer
- History of ultra-low HER2 expression: histopathology confirms ultra-low HER2 expression, defined as incomplete, faint membranous staining in ≤10% of invasive tumor cells.
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- If multiple historical/local HER2 test results are available for a subject, the most recent result derived from metastatic or advanced disease should be adopted.
- If local HER2 testing only classifies the subject's tumor as HER2-negative without available IHC status, the result must be re-confirmed by the Department of Pathology of Tianjin Medical University Cancer Institute and Hospital.
- Have radiographic or objective evidence of disease progression at or after the last prior systemic therapy before initiation of study treatment;
- For hormone-receptor-positive breast cancer: subjects have received 1-2 lines of endocrine therapy in the advanced-disease setting. Progression during adjuvant endocrine therapy or within 12 months after completion of adjuvant endocrine therapy counts as 1 prior line;
- For hormone-receptor-negative breast cancer: subjects have received 1-2 lines of prior systemic therapy. Progression during adjuvant therapy or within 12 months after completion of adjuvant therapy counts as 1 prior line;
- Have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1;
- Adequate major organ and bone marrow function meeting the following criteria:
- . Hemoglobin ≥90 g/L (no blood transfusion within 14 days);
- . Absolute neutrophil count ≥1.5×10⁹/L;
- . Platelet count ≥90×10⁹/L;
- . Total bilirubin ≤1.5 × upper limit of normal (ULN);
- . Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; in the presence of liver metastases, ALT and AST ≤5 × ULN;
- . Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min (calculated by the Cockcroft-Gault formula);
- . International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN;
- . Left ventricular ejection fraction (LVEF) ≥50%; QTc interval <470 ms for female subjects;
- Female subjects of child-bearing potential must agree to use highly effective contraception from study screening through 7 months after the last dose of study drug and agree not to breast-feed. A negative serum pregnancy test must be obtained within 7 days prior to the first study drug administration;
- No radiotherapy, chemotherapy, molecular-targeted therapy, immunotherapy or surgery within 4 weeks prior to enrollment; toxicities from prior therapies have recovered to Grade ≤1 (wounds fully healed if surgery was performed). No endocrine therapy within 14 days prior to enrollment.
- Subjects voluntarily participate in the study and provide written informed consent, with anticipated good compliance to follow protocol-required study procedures.
Who cannot join
- According to ASCO/CAP guidelines, subjects whose tumor has never been reported as HER2-positive (IHC 3+ or ISH-amplified);
- HR-positive patients who have received systemic chemotherapy in the advanced-disease setting;<br/>Prior anti-HER2 therapy; prior or ongoing treatment with antibody-drug conjugates containing exatecan derivatives (topoisomerase I inhibitors), including DS-8201a, Sacituzumab govitecan (SG), etc.;
- Known history of severe hypersensitivity to the drug substance, inactive ingredients in the pharmaceutical formulation, or other monoclonal antibodies;
- Received local radiotherapy, endocrine therapy, or oral small-molecule targeted anti-tumor therapy within 14 days prior to first study drug administration;
- received anti-tumor immunotherapy, macromolecular anti-tumor agents, or chemotherapy within 28 days prior to first study drug administration OR five half-lives (whichever is shorter). For oral fluoropyrimidines, folinic acid agents and weekly paclitaxel chemotherapy, the wash-out period shall be ≥14 days; for nitrosoureas and mitomycin, the wash-out period shall be ≥42 days. Underwent major surgery (e.g., trans-abdominal, trans-thoracic surgery; excluding diagnostic puncture, infusion-device implantation, biliary stent implantation and other minor procedures) within 28 days prior to first study drug administration, or anticipated to require major surgery during the study period
- Meningeal metastasis or active parenchymal brain metastasis. Subjects with clinically stable parenchymal brain metastasis may be enrolled, including asymptomatic brain metastases without prior local therapy; or subjects with previously treated CNS metastases (radiotherapy or surgery), provided radiological stability has been maintained for at least 4 weeks AND symptomatic treatment (including corticosteroids, mannitol, etc.) has been discontinued for more than 2 weeks.
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- Active brain metastasis: newly-diagnosed brain lesions without local therapy (surgery or radiotherapy), or radiologically progressive brain metastasis after prior treatment.
- Stable brain metastasis: brain metastasis with no radiological progression (no new lesions, no enlargement of existing lesions) for at least 4 weeks after local therapy (stereotactic radiotherapy, whole-brain radiotherapy or surgery);
- Other malignancies within the past 5 years, except for cured carcinoma in-situ of cervix, basal-cell carcinoma or squamous-cell carcinoma of skin (no treatment required for at least the past 3 years);
- Uncontrolled concurrent diseases, including but not limited to: persistent or active infection, uncontrolled or significant cardiovascular disease, severe chronic gastrointestinal disease accompanied by diarrhea, or psychiatric/social conditions that may compromise protocol compliance, substantially increase adverse-event risk, or impair the subject's ability to provide written informed consent;
- Uncontrolled or significant cardiovascular disease, defined by any of the following:
- History of myocardial infarction or symptomatic congestive heart failure (NYHA Class II-IV) within 6 months before enrollment. Subjects with troponin above ULN (per manufacturer reference range) without myocardial-infarction-related symptoms at screening shall receive cardiology consultation prior to enrollment to rule out myocardial infarction.
- Uncontrolled hypertension;
- Uncontrolled and/or clinically significant arrhythmia;
- Mean QTcF interval (QT corrected by Fredericia formula) >470 ms for female subjects, derived from three screening 12-lead ECGs;
- History of non-infectious interstitial lung disease (ILD)/non-infectious pneumonitis requiring steroid therapy; current ILD / non-infectious pneumonitis; or suspected ILD / non-infectious pneumonitis that cannot be excluded by imaging at screening;
- Clinically significant pulmonary comorbidities, including but not limited to underlying pulmonary diseases (i.e., pulmonary embolism within 3 months prior to screening, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, significant pleural effusion, etc.), autoimmune / connective-tissue / inflammatory diseases with pulmonary involvement (i.e., rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.), and/or prior complete pulmonary resection;
- Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes within 2 weeks before first study drug administration (dose >10 mg/day prednisone or equivalent physiological dose of other corticosteroids); nasal or inhaled corticosteroids are excluded;
- Active autoimmune disease, or history of autoimmune disease prone to relapse. Subjects with skin disorders not requiring systemic therapy (e.g., vitiligo, psoriasis, alopecia), well-controlled type 1 diabetes treated with insulin, or childhood-onset asthma fully resolved without adult-period intervention are eligible. Subjects requiring bronchodilator medical intervention for asthma are excluded;
- Uncontrolled infection requiring intravenous antibiotics, antiviral or antifungal agents;
- Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, active hepatitis B (HBsAg-positive with HBV DNA ≥500 IU/mL), or active hepatitis C infection. Among subjects with positive hepatitis C antibody, only those with negative HCV RNA by PCR are eligible;
- Received live-attenuated vaccine within 30 days prior to first study-drug administration (mRNA vaccines and non-replicating adenoviral vaccines are not regarded as live-attenuated vaccines). Note: If enrolled, subjects shall not receive live vaccines during the study and within 30 days after last study-drug dose;
- Unresolved toxicity from prior anti-cancer therapy, defined as toxicity not recovered to ≤Grade 1 or baseline (alopecia excluded).
- Note: Subjects with chronic stable Grade 2 toxicity judged by investigator to be related to prior anti-cancer therapy (defined as no deterioration to ≥Grade 2 for at least 3 months before enrollment and manageable with standard care) may be enrolled, e.g., chemotherapy-induced neuropathy, fatigue. Residual toxicities from prior immuno-oncology therapy including Grade 1 or 2 endocrine disorders are allowed: (a) hypothyroidism / hyperthyroidism; (b) type 1 diabetes mellitus; (c) hyperglycemia; (d) adrenal insufficiency; (e) adrenalitis; (f) skin depigmentation (vitiligo);
- Imaging demonstrates tumor encasement of major blood vessels, or investigator-judged high risk of tumor invasion into major blood vessels leading to life-threatening hemorrhage during treatment;
- Non-healing wounds or fractures for prolonged periods; major surgical procedures or severe traumatic injury, fracture or ulcer within 4 weeks prior to enrollment;
- Pregnant or lactating women; female subjects of child-bearing potential unwilling or unable to adopt effective contraceptive measures;
- Any other conditions judged by the investigator that may interfere with study conduct or endpoint assessment.
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, 1 recruiting
- Recruiting
Tianjin Medical University Cancer Institute and Hospital
Tianjin
About this study
Official title: A Single-Center, Single-Arm, Open-Label Phase II Study of SHR-A1811 in Patients With Advanced Breast Cancer With Ultra-Low HER2 Expression
This is a single-center, single-arm, open-label phase II exploratory study. A total of 30 patients aged 18-75 years with ECOG PS 0-1, pathologically confirmed advanced breast cancer with ultra-low HER2 expression will be enrolled. Eligible patients must have at least one measurable lesion and have received 1-2 lines of prior systemic therapy for advanced disease. All participants receive intravenous SHR-A1811 at 4.8 mg/kg every 3 weeks, until disease progression, intolerable adverse events or other discontinuation criteria. The primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), and safety profile.
- Being tested
- SHR- A1811
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHR- A1811Drug
4.8 mg/kg, intravenous infusion, administered every 3 weeks. Treatment continues until disease progression, intolerable adverse events, withdrawal of consent or death.
| Study group | Role | What they receive |
|---|---|---|
| SHR-A1811 Experimental Treatment Arm | Experimental | Not described Receives: Drug: SHR- A1811 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Response rate (CR+PR) assessed per RECIST Version 1.1
Measured: Up to 24 months
Secondary outcomes (5)
Progression-Free Survival (PFS)
Time from enrollment to disease progression or death, whichever occurs first, per RECIST Version 1.1
Measured: Time Frame: Up to 24 months
Overall Survival (OS)
Time from enrollment to death from any cause
Measured: Up to 24 months
Duration of Response (DOR)
Time from first documented CR/PR to disease progression or death, per RECIST Version 1.1
Measured: Up to 24 months
Disease Control Rate (DCR)
DCR defined as CR+PR+SD ≥6 weeks per RECIST Version 1.1
Measured: Up to 24 months
Clinical Benefit Rate (CBR)
CBR defined as CR+PR+SD ≥24 weeks per RECIST Version 1.1
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2026
- Study start1 Sep 2026
- Primary completion30 Sep 2028 (estimated)
- Study completion31 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Breast Cancer With Ultra-Low HER2 ExpressionStudies of the same condition, open and under way.
- More trials run by Tianjin Medical University Cancer Institute and HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07817082
- Sponsor's protocol ID
- OBUBC012
- Status last verified
- Sep 2026
- First submitted
- 8 Sep 2026
- Last updated
- 14 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Center, Single-Arm, Open-Label Phase II Study of SHR-A1811 in Patients With Advanced Breast Cancer With Ultra-Low HER2 Expression
- ClinicalTrials.gov ID
- NCT07817082
- Acronym / sponsor ID
- OBUBC012
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- 1 Sep 2026 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 31 Mar 2029 (estimated)
- First posted
- 14 Sep 2026 (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.
This is a single-center, single-arm, open-label phase II exploratory study. A total of 30 patients aged 18-75 years with ECOG PS 0-1, pathologically confirmed advanced breast cancer with ultra-low HER2 expression will be enrolled. Eligible patients must have at least one measurable lesion and have received 1-2 lines of prior systemic therapy for advanced disease. All participants receive intravenous SHR-A1811 at 4.8 mg/kg every 3 weeks, until disease progression, intolerable adverse events or other discontinuation criteria. The primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), and safety profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SHR-A1811 Experimental Treatment Arm | Experimental | Drug: SHR- A1811 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Female subjects, aged ≥18 years and ≤75 years;
- ECOG performance status 0-1;
- Expected survival of no less than 3 months;
- Histologically documented breast cancer:
- Have radiographic or objective evidence of disease progression at or after the last prior systemic therapy before initiation of study treatment;
Key exclusion criteria (28 listed)
- According to ASCO/CAP guidelines, subjects whose tumor has never been reported as HER2-positive (IHC 3+ or ISH-amplified);
- HR-positive patients who have received systemic chemotherapy in the advanced-disease setting;<br/>Prior anti-HER2 therapy; prior or ongoing treatment with antibody-drug conjugates containing exatecan derivatives (topoisomerase I inhibitors), including DS-8201a, Sacituzumab govitecan (SG), etc.;
- Known history of severe hypersensitivity to the drug substance, inactive ingredients in the pharmaceutical formulation, or other monoclonal antibodies;
- Received local radiotherapy, endocrine therapy, or oral small-molecule targeted anti-tumor therapy within 14 days prior to first study drug administration;
- received anti-tumor immunotherapy, macromolecular anti-tumor agents, or chemotherapy within 28 days prior to first study drug administration OR five half-lives (whichever is shorter). For oral fluoropyrimidines, folinic acid agents and weekly paclitaxel chemotherapy, the wash-out period shall be ≥14 days; for nitrosoureas and mitomycin, the wash-out period shall be ≥42 days. Underwent major surgery (e.g., trans-abdominal, trans-thoracic surgery; excluding diagnostic puncture, infusion-device implantation, biliary stent implantation and other minor procedures) within 28 days prior to first study drug administration, or anticipated to require major surgery during the study period
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 |
|---|---|---|
| SHR- A18114.8 mg/kg, intravenous infusion, administered every 3 weeks. Treatment continues until disease progression, intolerable adverse events, withdrawal of consent or death. | Drug | SHR-A1811 Experimental Treatment Arm |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 24 months
Response rate (CR+PR) assessed per RECIST Version 1.1
5 secondary outcomes
Progression-Free Survival (PFS)
Time frame: Time Frame: Up to 24 months
Overall Survival (OS)
Time frame: Up to 24 months
Duration of Response (DOR)
Time frame: Up to 24 months
Disease Control Rate (DCR)
Time frame: Up to 24 months
Clinical Benefit Rate (CBR)
Time frame: Up to 24 months
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 14 Sep 2026.
- Individual participant dataSharing planned: No
Related trials for Advanced Breast Cancer With Ultra-Low HER2 Expression
Not yet recruitingObservational study
The Efficacy of Combined Peripheral Blood CTCs and Serum HER2 Detection in Docetaxel-based Treatment for HER2 Low-expression Breast Cancer
Patients With Low HER2 Expression (IHC 1+ or IHC 2+/ISH-) and HER2 IHC 0 Advanced Breast Cancer
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SHR- A1811 in people with Advanced Breast Cancer With Ultra-Low HER2 Expression, run by Tianjin Medical University Cancer Institute and Hospital 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 24 inclusion and 28 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: looking for participants now, as of the sponsor's last update on 14 Sep 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Xu Wang (+86-18622221185, wxuxu@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 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 14 Sep 2026.