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

NCT07856303 | Not Yet Recruiting Phase 2

• 1 other identifier: SCHBCC-N0123
• Study Type: interventional
• Target: 358
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

HER2-positive Breast Cancer; Early Breast Cancer (EBC)

Keywords

Circulating Tumor DNA; ctDNA; Minimal Residual Disease; Pathologic Complete Response; Adjuvant Therapy; SHR-A1811

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Distant Disease-Free Survival (DDFS)

  Up to 5 years after randomization

• Overall Survival (OS)

  Up to 5 years after randomization

• Brain Metastasis-Free Interval (BMFI)

  Up to 5 years after randomization

• Treatment-Emergent Adverse Events

  From randomization through 40 days after the last dose of study treatment

Study Arms (2)

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.

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.

Drug: Trastuzumab; Drug: Pertuzumab

Interventions

SHR-A1811 DRUG

4.8 mg/kg by intravenous infusion once every 3 weeks for 14 cycles.

SHR-A1811

Trastuzumab DRUG

Loading dose: 8 mg/kg IV. Maintenance dose: 6 mg/kg IV Q3W.

Trastuzumab Plus Pertuzumab

Pertuzumab DRUG

Loading dose: 840 mg IV. Maintenance dose: 420 mg IV Q3W.

Trastuzumab Plus Pertuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai

Shanghai, China

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm, Residual; Pathologic Complete Response

Interventions

Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Progression; Disease Attributes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Zhimin Shao

CONTACT

86-021-64175590; zhimingshao@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Model Details: 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)

Study Record Dates

• First Submitted: September 28, 2026
• First Posted: October 2, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): August 1, 2032
• Study Completion (Estimated): August 1, 2034
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)