HER2-positive Breast CancerPhase 2NCT07856303
SHR-A1811 Versus Trastuzumab Plus Pertuzumab in ctDNA-Positive HER2-Positive Early Breast Cancer After Pathologic Complete Response
A Phase 2 study testing SHR-A1811, Trastuzumab and Pertuzumab in people with HER2-positive Breast Cancer and Early Breast Cancer (EBC), run by Fudan University at 1 site in China.
Trial summary
This investigator-initiated, single-center, randomized, open-label, phase II trial will evaluate the efficacy and safety of intensified adjuvant SHR-A1811 compared with trastuzumab plus pertuzumab in women with initially stage IIB-IIIC HER2-positive early breast cancer who achieved pathologic complete response after… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive Breast Cancer, Early Breast Cancer (EBC)
- What is being tested?
- SHR-A1811, Trastuzumab and Pertuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 358 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2026to Aug 2034
- Phase
- Phase 2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent before any study-specific procedure and willingness to comply with study visits and sample collection.
- Female, aged 18 years or older.
- Histologically confirmed invasive breast carcinoma at initial diagnosis, without distant metastasis.
- HER2-positive tumor at initial diagnosis, defined as IHC 3+ or IHC 2+ with ISH amplification; hormone receptor status must be known.
- Initial clinical anatomic stage IIB-IIIC according to the AJCC 8th edition.
- Completion of at least 6 cycles and at least 16 weeks of standard neoadjuvant systemic therapy.
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- Definitive breast surgery and appropriate axillary staging or dissection, with pathologically complete resection.
- Pathologic complete response, defined as no residual invasive carcinoma in the breast or regional lymph nodes (ypT0/is ypN0); residual ductal carcinoma in situ is permitted.
- Postoperative ctDNA positivity confirmed by the designated central testing laboratory 14-42 days after the last definitive surgery and before initiation of any adjuvant systemic therapy.
- No clinical, pathologic, or radiographic evidence of locoregional recurrence or distant metastasis before randomization; baseline chest CT is required to assess interstitial lung disease/noninfectious pneumonitis.
- Randomization within 12 weeks after the last definitive surgery; extension to 14 weeks may be permitted for documented surgical complications, reoperation, or sequential radiotherapy with principal investigator approval.
- ECOG performance status 0 or 1.
- Left ventricular ejection fraction at least 50% within 28 days before randomization, without clinically significant cardiac dysfunction.
- Adequate bone marrow, hepatic, renal, and coagulation function.
- Negative pregnancy test for participants of childbearing potential and agreement to use highly effective contraception for the protocol-specified period.
Who cannot join
- Clinical, radiographic, or pathologic evidence of unresectable locally advanced, recurrent, or metastatic disease, or disease progression during neoadjuvant therapy.
- Failure to achieve ypT0/is ypN0 or any residual invasive carcinoma in the breast or regional lymph nodes.
- Prior ipsilateral or contralateral breast cancer, including ductal carcinoma in situ; lobular carcinoma in situ is permitted.
- Any postoperative systemic anticancer therapy before randomization, including trastuzumab, pertuzumab, another anti-HER2 agent, chemotherapy, antibody-drug conjugate, or endocrine therapy; bridging therapy is not permitted.
- Prior neoadjuvant treatment with T-DM1, trastuzumab deruxtecan, SHR-A1811, or another HER2-directed antibody-drug conjugate.
- Prior or current interstitial lung disease/noninfectious pneumonitis requiring corticosteroid treatment, active interstitial lung disease on screening imaging, clinically significant pulmonary fibrosis, severe chronic obstructive pulmonary disease, resting hypoxemia, or another pulmonary disorder that would interfere with pulmonary toxicity assessment.
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- Clinically significant cardiovascular disease, including symptomatic heart failure or NYHA class II-IV heart failure, myocardial infarction or unstable angina within 6 months before screening, uncontrolled clinically significant arrhythmia, QTcF greater than 470 ms, or blood pressure above 150/90 mmHg despite appropriate treatment.
- Active or uncontrolled infection requiring systemic treatment, or active HBV/HCV or HIV not meeting protocol and institutional control criteria.
- Toxicities from prior therapy not recovered to grade 1 or lower, except alopecia, hyperpigmentation, and stable grade 2 peripheral neuropathy judged clinically insignificant by the investigator.
- Another malignancy within 5 years before screening, except adequately treated basal or squamous cell skin cancer, cervical carcinoma in situ, or another malignancy with a low risk of recurrence.
- Severe hypersensitivity to a study drug or any of its excipients.
- Pregnancy, breastfeeding, or plans for pregnancy during the protocol-specified period.
- Any serious medical or psychosocial condition that, in the investigator's judgment, would make study treatment, follow-up, or interpretation of results unsafe or unreliable.
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
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai
Shanghai
Zhimin Shao, 86-021-641755901105, zhimingshao@yahoo.com
Lei Fan, 86-021-641755901105, cmchen@medmail.com.cn
About this study
Official title: A Randomized, Open-Label, Phase II Study of Intensified Adjuvant SHR-A1811 Versus Trastuzumab Plus Pertuzumab in Patients With Initially Stage IIB-IIIC HER2-Positive Early Breast Cancer Who Achieved Pathologic Complete Response After Neoadjuvant Therapy and Have Postoperative ctDNA Positivity
This investigator-initiated, single-center, randomized, open-label, phase II trial will evaluate the efficacy and safety of intensified adjuvant SHR-A1811 compared with trastuzumab plus pertuzumab in women with initially stage IIB-IIIC HER2-positive early breast cancer who achieved pathologic complete response after neoadjuvant systemic therapy and have detectable postoperative circulating tumor DNA (ctDNA). Eligible participants will be randomized 1:1 and stratified by hormone receptor status, HER2 test category, and initial clinical anatomic stage. The primary endpoint is invasive disease-free survival.
Read the detailed description
Patients who have completed neoadjuvant systemic therapy and curative breast and axillary surgery with ypT0/is ypN0 disease will undergo postoperative ctDNA testing 14 to 42 days after the last definitive surgery and before initiation of adjuvant systemic therapy. Participants with ctDNA positivity and no clinical or radiographic evidence of recurrent or metastatic disease will be randomized to SHR-A1811 or trastuzumab plus pertuzumab. Post-randomization ctDNA results will not be used for clinical management and will remain blinded to investigators and participants until the primary analysis database is locked, unless a future ethics-approved protocol amendment specifies otherwise.
- Being tested
- SHR-A1811, Trastuzumab, Pertuzumab
- Keywords
- Circulating Tumor DNA, ctDNA, Minimal Residual Disease, Pathologic Complete Response, Adjuvant Therapy, SHR-A1811
- Medical subject headings
- Breast Neoplasms, Neoplasm, Residual, Pathologic Complete Response
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 by intravenous infusion once every 3 weeks for 14 cycles.
TrastuzumabDrug
Loading dose: 8 mg/kg IV. Maintenance dose: 6 mg/kg IV Q3W.
PertuzumabDrug
Loading dose: 840 mg IV. Maintenance dose: 420 mg IV Q3W.
| Study group | Role | What they receive |
|---|---|---|
| SHR-A1811 | Experimental | Participants will receive SHR-A1811 4.8 mg/kg by intravenous infusion once every 3 weeks for 14 cycles. Dose interruption and reduction will be managed according to the protocol and study drug management instructions. Receives: Drug: SHR-A1811 |
| Trastuzumab Plus Pertuzumab | Active comparator | Participants will receive trastuzumab plus pertuzumab once every 3 weeks. Including treatment received during the neoadjuvant period, the total perioperative duration of dual HER2-targeted therapy will be approximately 1 year. Receives: Drug: Trastuzumab; Drug: Pertuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Invasive Disease-Free Survival (IDFS)
IDFS is defined as the time from randomization to the first occurrence of ipsilateral invasive breast tumor recurrence, regional invasive recurrence, distant recurrence, contralateral invasive breast cancer, secondary invasive primary cancer (nonbreast), or death from any cause.
Measured: At 3 years after randomization
Secondary outcomes (4)
Distant Disease-Free Survival (DDFS)
DDFS is defined as the time from randomization to the first occurrence of distant recurrence, secondary invasive primary cancer (nonbreast), or death from any cause.
Measured: Up to 5 years after randomization
Overall Survival (OS)
Time from randomization to death from any cause.
Measured: Up to 5 years after randomization
Brain Metastasis-Free Interval (BMFI)
Time from randomization to brain metastasis
Measured: Up to 5 years after randomization
Treatment-Emergent Adverse Events
Number and percentage of participants with treatment-emergent adverse events and serious adverse events, graded according to NCI CTCAE version 5.0.
Measured: From randomization through 40 days after the last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2026
- Study start1 Oct 2026 (estimated)
- Primary completionAug 2032 (estimated)
- Study completionAug 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized 1:1 to SHR-A1811 or trastuzumab plus pertuzumab. Randomization will be stratified by hormone receptor status (positive vs negative), HER2 status (IHC 3+ vs IHC 2+/ISH-positive), and initial clinical anatomic stage (IIB vs III)
- Masking
- None (open label)
- Enrolment
- 358 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhimin Shao, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07856303
- Sponsor's protocol ID
- SCHBCC-N0123
- Status last verified
- Sep 2026
- First submitted
- 28 Sep 2026
- Last updated
- 2 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No