SHR-A1811 Versus Trastuzumab Plus Pertuzumab in ctDNA-Positive HER2-Positive Early Breast Cancer After Pathologic Complete Response

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HER2-positive Breast Cancer; Early Breast Cancer (EBC)
• Intervention / Treatment: Drug: SHR-A1811; Drug: Trastuzumab; Drug: Pertuzumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 358
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhimin Shao; Phone Number: 8888 86-021-64175590; Email: zhimingshao@yahoo.com

Study Locations

• China
  • Shanghai, China
    • Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai
    • Contact: Zhimin Shao; Phone Number: 86-021-641755901105; Email: zhimingshao@yahoo.com
    • Contact: Lei Fan; Phone Number: 86-021-641755901105; Email: cmchen@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent before any study-specific procedure and willingness to comply with study visits and sample collection.
2. Female, aged 18 years or older.
3. Histologically confirmed invasive breast carcinoma at initial diagnosis, without distant metastasis.
4. HER2-positive tumor at initial diagnosis, defined as IHC 3+ or IHC 2+ with ISH amplification; hormone receptor status must be known.
5. Initial clinical anatomic stage IIB-IIIC according to the AJCC 8th edition.
6. Completion of at least 6 cycles and at least 16 weeks of standard neoadjuvant systemic therapy.
7. Definitive breast surgery and appropriate axillary staging or dissection, with pathologically complete resection.
8. 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.
9. 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.
10. 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.
11. 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.
12. ECOG performance status 0 or 1.
13. Left ventricular ejection fraction at least 50% within 28 days before randomization, without clinically significant cardiac dysfunction.
14. Adequate bone marrow, hepatic, renal, and coagulation function.
15. Negative pregnancy test for participants of childbearing potential and agreement to use highly effective contraception for the protocol-specified period.

Exclusion Criteria:

1. Clinical, radiographic, or pathologic evidence of unresectable locally advanced, recurrent, or metastatic disease, or disease progression during neoadjuvant therapy.
2. Failure to achieve ypT0/is ypN0 or any residual invasive carcinoma in the breast or regional lymph nodes.
3. Prior ipsilateral or contralateral breast cancer, including ductal carcinoma in situ; lobular carcinoma in situ is permitted.
4. 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.
5. Prior neoadjuvant treatment with T-DM1, trastuzumab deruxtecan, SHR-A1811, or another HER2-directed antibody-drug conjugate.
6. 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.
7. 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.
8. Active or uncontrolled infection requiring systemic treatment, or active HBV/HCV or HIV not meeting protocol and institutional control criteria.
9. 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.
10. 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.
11. Severe hypersensitivity to a study drug or any of its excipients.
12. Pregnancy, breastfeeding, or plans for pregnancy during the protocol-specified period.
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-A1811; 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.	Drug: SHR-A1811; 4.8 mg/kg by intravenous infusion once every 3 weeks for 14 cycles.
Active Comparator: Trastuzumab Plus Pertuzumab; 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.	Drug: Trastuzumab; Loading dose: 8 mg/kg IV. Maintenance dose: 6 mg/kg IV Q3W.; Drug: Pertuzumab; Loading dose: 840 mg IV. Maintenance dose: 420 mg IV Q3W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 3 years after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 5 years after randomization
Overall Survival (OS)	Time from randomization to death from any cause.	Up to 5 years after randomization
Brain Metastasis-Free Interval (BMFI)	Time from randomization to brain metastasis	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.	From randomization through 40 days after the last dose of study treatment

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): August 1, 2032
• Study Completion (Estimated): August 1, 2034

Study Registration Dates

• First Submitted: September 28, 2026
• First Submitted That Met QC Criteria: September 28, 2026
• First Posted (Actual): October 2, 2026

Study Record Updates

• Last Update Posted (Actual): October 2, 2026
• Last Update Submitted That Met QC Criteria: September 28, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: ctDNA; Pathologic Complete Response; Circulating Tumor DNA; Adjuvant Therapy; Minimal Residual Disease; SHR-A1811
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Neoplastic Processes; Skin Diseases; Breast Diseases; Disease Progression; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Pathologic Complete Response; Neoplasm, Residual; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Trastuzumab; pertuzumab
• Other Study ID Numbers: SCHBCC-N0123

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No