SHR-A1811Phase 2NCT07307287
SHR-A1811 Plus Pertuzumab as Neoadjuvant Therapy for Early or Locally Advanced HR-Positive HER2-Positive Breast Cancer: A Prospective, Open-Label, Phase II Study
A Phase 2 study testing SHR- A1811 in people with SHR-A1811 and HER2-Postive Breast Cancer, run by Tianjin Medical University Cancer Institute and Hospital.
Trial summary
Breast cancer is the most common malignancy in women, with approximately 20% classified as HER2-positive. Anti-HER2 blockade (trastuzumab plus pertuzumab) combined with chemotherapy constitutes the standard neoadjuvant regimen; however, the pathological complete response (pCR) rate in the HR-positive subgroup remains… Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- SHR-A1811, HER2-Postive Breast Cancer, HR+ Breast Cancer
- 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
- No sites listed yet
- Study dates
- 20 Dec 2025to 31 Dec 2027
- 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, aged 18-70 years at the time of informed consent.
- Histologically confirmed invasive breast cancer, with no prior systemic anti-cancer therapy.
- Pathologically documented HR-positive (ER ≥ 1% and/or PR ≥ 1%) and HER2-positive disease, per the 2018 ASCO-CAP guidelines: IHC 3+ or IHC 2+ with ISH ratio ≥ 2.0.
- Clinical stage II-III (cT2-cT4 or cN+, cM0) per the 8th edition of the AJCC Cancer Staging Manual.
- At least one measurable lesion per RECIST v1.1 criteria.
- ECOG performance status 0-1.
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- Estimated life expectancy of ≥ 12 months.
- Adequate organ function within 14 days prior to the first dose (without transfusion or growth factor support):
- Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelets ≥ 100 × 10⁹/L; hemoglobin (Hb) ≥ 90 g/L
- Albumin ≥ 3.0 g/dL; total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); alanine transaminase (ALT)/aspartate transaminase (AST) ≤ 2.5 × ULN; alkaline phosphatase (ALP) ≤ 2.5 × ULN; blood urea nitrogen (BUN) and creatinine ≤ 1.5 × ULN, or creatinine clearance (CrCl) ≥ 60 mL/min (per Cockcroft-Gault formula)
- Prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
- Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiography
- Fridericia-corrected QT interval (QTcF) ≤ 470 ms
- Premenopausal women with reproductive potential must have a negative serum β-human chorionic gonadotropin (β-hCG) test within 7 days before treatment, use effective barrier contraception throughout the study period and for 6 months after the last dose, and not be breastfeeding.
- Provision of signed written informed consent; willingness to comply with all study visits and procedures.
Who cannot join
- Breast cancer not confirmed by histopathology.
- Bilateral, inflammatory, or occult breast cancer.
- Any prior anti-cancer therapy (chemotherapy, radiotherapy, targeted, endocrine, etc.); radical radiotherapy ≤ 4 weeks or palliative radiotherapy ≤ 2 weeks before first dose.
- Concomitant anti-cancer therapy of any kind.
- Other malignancies within 5 years (except cured basal-cell skin cancer or cervical carcinoma in situ).
- Participation in another drug trial ≤ 4 weeks before enrolment.
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- Systemic immunosuppressive therapy (e.g., > 10 mg/day prednisone equivalent) ≤ 2 weeks before first dose (nasal/inhaled corticosteroids allowed).
- Live or attenuated vaccines ≤ 4 weeks before first dose.
- Major non-breast surgery ≤ 4 weeks before first dose or not fully recovered.
- Active autoimmune disease or history of recurrent autoimmunity (e.g., autoimmune hepatitis, uveitis, colitis, hypophysitis, vasculitis, nephritis, hyper/hypothyroidism except stable hormone replacement). Controlled vitiligo, psoriasis, alopecia, insulin-dependent type 1 diabetes, or childhood asthma in complete remission allowed. Asthma requiring bronchodilators excluded.
- Immunodeficiency (HIV positive, congenital/secondary), prior organ transplant.
- Uncontrolled or significant cardiovascular/cerebrovascular disease, including within 6 months: NYHA III/IV heart failure, MI, stroke (except lacunar), pulmonary embolism, unstable angina, significant arrhythmia; cardiomyopathies; QTc > 470 ms (Fridericia, female), 2nd/3rd degree AV block, atrial fibrillation ≥ EHRA 2b, uncontrolled hypertension.
- Interstitial lung disease or any moderate-severe pulmonary disorder that may interfere with drug-related lung toxicity assessment: idiopathic pulmonary fibrosis, organizing pneumonia/bronchiolitis obliterans, pulmonary embolism, severe asthma/COPD, restrictive/obstructive defects, autoimmune/connective-tissue lung involvement, prior pneumonectomy.
- Active hepatitis B (HBsAg+ and HBV DNA ≥ 500 IU/mL), hepatitis C (anti-HCV+ and HCV RNA > ULN), cirrhosis, or severe infection requiring antibiotics/antivirals/antifungals.
- Hereditary/acquired bleeding or thrombotic diatheses (e.g., hemophilia, coagulopathy).
- Known hypersensitivity to study drugs or excipients.
- Pregnant or lactating women; women of child-bearing potential with positive baseline pregnancy test or unwilling to use effective contraception throughout the study.
- Any severe concomitant condition jeopardizing patient safety or compliance (e.g., uncontrolled hypertension, diabetes, active infection) or significant neurologic/psychiatric disorder (epilepsy, dementia) that, in the investigator's opinion, renders
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Breast cancer is the most common malignancy in women, with approximately 20% classified as HER2-positive. Anti-HER2 blockade (trastuzumab plus pertuzumab) combined with chemotherapy constitutes the standard neoadjuvant regimen; however, the pathological complete response (pCR) rate in the HR-positive subgroup remains only 35-40%, and platinum-containing schedules are associated with significant hematologic toxicity. Antibody-drug conjugates (ADCs) integrate targeted delivery with potent cytotoxic payloads. SHR-A1811 (ruikang-trastuzumab), a domestically developed ADC by Hengrui Pharmaceutical, is conjugated with a topoisomerase I inhibitor (mean drug-to-antibody ratio [DAR] ≈ 6). Preclinical data demonstrate that SHR-A1811 exhibits superior efficacy to trastuzumab emtansine (T-DM1) in both trastuzumab-sensitive and resistant HER2-expressing tumor models, with a manageable safety profile.
This prospective, open-label, phase II trial will enroll patients with early-stage/locally advanced HR-positive/HER2-positive breast cancer, who will receive neoadjuvant SHR-A1811 plus pertuzumab. At baseline, BluePrint gene profiling will be performed to stratify participants into luminal and non-luminal subtypes: patients with luminal subtype who achieve stable disease (SD) after 4 cycles will switch to a regimen of trastuzumab, pyrotinib, dalpiciclib, and an aromatase inhibitor for an additional 4 cycles; all other patients will continue ADC-based dual-target therapy for 2-4 further cycles, followed by surgical resection. Circulating tumor DNA (ctDNA) dynamics will be dynamically monitored at baseline, after 4 cycles of treatment, and preoperatively to evaluate early treatment sensitivity.
The primary endpoint is the pCR rate. Secondary endpoints include event-free survival (EFS), objective response rate (ORR), and safety profiles. Exploratory analyses will investigate the correlation between molecular subtypes and treatment responses, aiming to establish a chemotherapy-free, precision neoadjuvant strategy for HR-positive/HER2-positive breast cancer.
- Conditions
- SHR-A1811, HER2-Postive Breast Cancer, HR+ Breast Cancer, Early Breast Cancer, Locally Advanced Breast Cancer
- Being tested
- SHR- A1811
- Keywords
- SHR-A1811, HER2-Postive Breast Cancer, HR+ Breast Cancer, Early Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHR- A1811Drug
Also called Pyrotinib, Dalpiciclib
SHR-A1811 4.8 mg/kg and pertuzumab 420 mg are administered intravenously every 3 weeks for 4 cycles as neoadjuvant therapy. Patients with luminal subtype and stable disease (SD) then switch to trastuzumab 6 mg/kg, pyrotinib 320 mg po daily, dalpiciclib 125 mg po days 1-21 of a 28-day cycle, plus an aromatase inhibitor for 4 additional cycles. All remaining patients (PR/CR luminal or any non-luminal) continue SHR-A1811 + pertuzumab for 2-4 more cycles before surgery. Treatment continues until progression, unacceptable toxicity, or surgical resection.
| Study group | Role | What they receive |
|---|---|---|
| SHR-A1811 + Pertuzumab Neoadjuvant Therapy for HER2+ HR+ Breast Cancer | Experimental | All patients to be included in the analysis must undergo Blueprint genomic profiling before neoadjuvant therapy to define luminal and non-luminal molecular subtypes. After completing four cycles of neoadjuvant therapy with ruikang-trastuzumab plus pertuzumab, response is assessed by RECIST 1.1:
1. Patients with stable disease (SD) and luminal subtype switch to a quadruplet regimen of trastuzumab, pyrotinib, dalpiciclib, and an aromatase inhibitor for a further four cycles.
2. Patients achieving partial or complete response (PR/CR) and luminal subtype, as well as all non-luminal patients, continue ruikang-trastuzumab plus pertuzumab for an additional 2-4 cycles, tailored to individual clinical response, before undergoing surgery Receives: Drug: SHR- A1811 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic complete response (pCR)
Percentage of patients with no invasive cancer in the breast and axillary lymph nodes (ypT0/is ypN0) at definitive surgery.
Measured: At the time of definitive surgery, approximately 24 weeks after study entry
Secondary outcomes (3)
5-year Event-free survival (EFS)
5 years event-free survival after surgery
Measured: 60 weeks
Objective response rate (ORR)
Proportion of patients achieving complete or partial response (CR + PR) by RECIST 1.1 after neoadjuvant therapy.
Measured: 18 weeks
Safety and tolerability
Incidence and severity of adverse events graded by CTCAE v5.0 from first dose up to 30 days after last dose.
Measured: From enrollment to the end of treatment at 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2025
- Study start20 Dec 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 SHR-A1811Studies 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
- NCT07307287
- Sponsor's protocol ID
- OBU-BC-II-280
- Status last verified
- Dec 2025
- First submitted
- 2 Dec 2025
- Last updated
- 29 Dec 2025
- 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 29 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SHR-A1811 Plus Pertuzumab as Neoadjuvant Therapy for Early or Locally Advanced HR-Positive HER2-Positive Breast Cancer: A Prospective, Open-Label, Phase II Study
- ClinicalTrials.gov ID
- NCT07307287
- Acronym / sponsor ID
- OBU-BC-II-280
- Conditions
- SHR-A1811, HER2-Postive Breast Cancer, HR+ Breast Cancer, Early Breast Cancer, Locally Advanced Breast Cancer
- Keywords
- SHR-A1811, HER2-Postive Breast Cancer, HR+ Breast Cancer, Early Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- 20 Dec 2025 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 29 Dec 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.
Breast cancer is the most common malignancy in women, with approximately 20% classified as HER2-positive. Anti-HER2 blockade (trastuzumab plus pertuzumab) combined with chemotherapy constitutes the standard neoadjuvant regimen; however, the pathological complete response (pCR) rate in the HR-positive subgroup remains only 35-40%, and platinum-containing schedules are associated with significant hematologic toxicity. Antibody-drug conjugates (ADCs) integrate targeted delivery with potent cytotoxic payloads. SHR-A1811 (ruikang-trastuzumab), a domestically developed ADC by Hengrui Pharmaceutical, is conjugated with a topoisomerase I inhibitor (mean drug-to-antibody ratio [DAR] ≈ 6). Preclinical data demonstrate that SHR-A1811 exhibits superior efficacy to trastuzumab emtansine (T-DM1) in both trastuzumab-sensitive and resistant HER2-expressing tumor models, with a manageable safety profile.
This prospective, open-label, phase II trial will enroll patients with early-stage/locally advanced HR-positive/HER2-positive breast cancer, who will receive neoadjuvant SHR-A1811 plus pertuzumab. At baseline, BluePrint gene profiling will be performed to stratify participants into luminal and non-luminal subtypes: patients with luminal subtype who achieve stable disease (SD) after 4 cycles will switch to a regimen of trastuzumab, pyrotinib, dalpiciclib, and an aromatase inhibitor for an additional 4 cycles; all other patients will continue ADC-based dual-target therapy for 2-4 further cycles, followed by surgical resection. Circulating tumor DNA (ctDNA) dynamics will be dynamically monitored at baseline, after 4 cycles of treatment, and preoperatively to evaluate early treatment sensitivity.
The primary endpoint is the pCR rate. Secondary endpoints include event-free survival (EFS), objective response rate (ORR), and safety profiles. Exploratory analyses will investigate the correlation between molecular subtypes and treatment responses, aiming to establish a chemotherapy-free, precision neoadjuvant strategy for HR-positive/HER2-positive breast cancer.
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 + Pertuzumab Neoadjuvant Therapy for HER2+ HR+ Breast Cancer | Experimental | Drug: SHR- A1811All patients to be included in the analysis must undergo Blueprint genomic profiling before neoadjuvant therapy to define luminal and non-luminal molecular subtypes. After completing four cycles of neoadjuvant therapy with ruikang-trastuzumab plus pertuzumab, response is assessed by RECIST 1.1: 1. Patients with stable disease (SD) and luminal subtype switch to a quadruplet regimen of trastuzumab, pyrotinib, dalpiciclib, and an aromatase inhibitor for a further four cycles. 2. Patients achieving partial or complete response (PR/CR) and luminal subtype, as well as all non-luminal patients, continue ruikang-trastuzumab plus pertuzumab for an additional 2-4 cycles, tailored to individual clinical response, before undergoing surgery |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Female, aged 18-70 years at the time of informed consent.
- Histologically confirmed invasive breast cancer, with no prior systemic anti-cancer therapy.
- Pathologically documented HR-positive (ER ≥ 1% and/or PR ≥ 1%) and HER2-positive disease, per the 2018 ASCO-CAP guidelines: IHC 3+ or IHC 2+ with ISH ratio ≥ 2.0.
- Clinical stage II-III (cT2-cT4 or cN+, cM0) per the 8th edition of the AJCC Cancer Staging Manual.
- At least one measurable lesion per RECIST v1.1 criteria.
Key exclusion criteria (18 listed)
- Breast cancer not confirmed by histopathology.
- Bilateral, inflammatory, or occult breast cancer.
- Any prior anti-cancer therapy (chemotherapy, radiotherapy, targeted, endocrine, etc.); radical radiotherapy ≤ 4 weeks or palliative radiotherapy ≤ 2 weeks before first dose.
- Concomitant anti-cancer therapy of any kind.
- Other malignancies within 5 years (except cured basal-cell skin cancer or cervical carcinoma in situ).
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- A1811Also: Pyrotinib, DalpiciclibSHR-A1811 4.8 mg/kg and pertuzumab 420 mg are administered intravenously every 3 weeks for 4 cycles as neoadjuvant therapy. Patients with luminal subtype and stable disease (SD) then switch to trastuzumab 6 mg/kg, pyrotinib 320 mg po daily, dalpiciclib 125 mg po days 1-21 of a 28-day cycle, plus an aromatase inhibitor for 4 additional cycles. All remaining patients (PR/CR luminal or any non-luminal) continue SHR-A1811 + pertuzumab for 2-4 more cycles before surgery. Treatment continues until progression, unacceptable toxicity, or surgical resection. | Drug | SHR-A1811 + Pertuzumab Neoadjuvant Therapy for HER2+ HR+ Breast Cancer |
Primary outcome
Pathologic complete response (pCR)
Time frame: At the time of definitive surgery, approximately 24 weeks after study entry
Percentage of patients with no invasive cancer in the breast and axillary lymph nodes (ypT0/is ypN0) at definitive surgery.
3 secondary outcomes
5-year Event-free survival (EFS)
Time frame: 60 weeks
Objective response rate (ORR)
Time frame: 18 weeks
Safety and tolerability
Time frame: From enrollment to the end of treatment at 8 weeks
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 29 Dec 2025.
- Individual participant dataSharing planned: No
Related trials for SHR-A1811
Not yet recruitingPhase 2
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Breast Cancer, Serplulimab Combined With SHR-A1811 as Neoadjuvant Therapy for Triple-Negative 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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SHR- A1811 in people with SHR-A1811 and HER2-Postive Breast Cancer, run by Tianjin Medical University Cancer Institute and Hospital.
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 15 inclusion and 18 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 29 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
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 Xuchen Cao (+86+022-23109106, caoxuchen@tmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic complete response (pCR) (time frame: At the time of definitive surgery, approximately 24 weeks after study entry). 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 29 Dec 2025; AzTrials last refreshed its copy on 6 Nov 2026.