Phase II Study of SHR-A1811 for Ultra-Low HER2 Advanced Breast Cancer

NCT07817082 | Recruiting Phase 2

• 1 other identifier: OBUBC012
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Advanced Breast Cancer With Ultra-Low HER2 Expression

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Response rate (CR+PR) assessed per RECIST Version 1.1

  Up to 24 months

Secondary Outcomes (5)

• Progression-Free Survival (PFS)

  Time Frame: Up to 24 months

• Overall Survival (OS)

  Up to 24 months

• Duration of Response (DOR)

  Up to 24 months

• Disease Control Rate (DCR)

  Up to 24 months

• Clinical Benefit Rate (CBR)

  Up to 24 months

Study Arms (1)

SHR-A1811 Experimental Treatment Arm

EXPERIMENTAL

Drug: SHR- A1811

Interventions

SHR- A1811 DRUG

4.8 mg/kg, intravenous infusion, administered every 3 weeks. Treatment continues until disease progression, intolerable adverse events, withdrawal of consent or death.

SHR-A1811 Experimental Treatment Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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;

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, China

RECRUITING

Central Study Contacts

Xu Wang

CONTACT

+86-18622221185; wxuxu@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2026
• First Posted: September 14, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: September 14, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)