Breast CancerPhase 1/2NCT07177950
A Two-cohort Study of SHR-A1811 in the Treatment of HER2-positive Breast Cancer With Brain Metastases
A Phase 1/2 study testing SHR-A1811 and radiotherapy in people with Breast Cancer and Brain Metastases, run by Peking University Cancer Hospital & Institute.
Trial summary
This is a multi-center, open-label, two-cohort study. The purpose of this study is to evaluate the safety, tolerability and efficacy of SHR-A1811 in the treatment of HER2-positive breast cancer with brain and leptomeningeal metastases, and the efficacy and safety of SHR-A1811 in the treatment of HER2-positive breast… Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Breast Cancer, Brain Metastases, Leptomeningeal Metastasis
- What is being tested?
- SHR-A1811 and radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2025to 30 Sep 2029
- Phase
- Phase 1/2
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 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women aged 18-75 years (inclusive).
- Histologically or cytologically confirmed HER2-positive advanced breast cancer (IHC 3+, or IHC 2+ with ISH amplification).
- Radiologically documented brain metastases, with or without baseline leptomeningeal disease:
- Cohort A (leptomeningeal metastasis cohort): leptomeningeal involvement demonstrated by contrast-enhanced MRI or positive cerebrospinal fluid (CSF) cytology.
- Cohort B (no leptomeningeal metastasis cohort): ≥1 measurable intracranial lesion; either CNS-naïve or progressive after prior local therapy.
- Anticipated life expectancy >12 weeks.
Show all 15Show fewer
- ECOG performance status 0-2.
- Adequate organ function as defined by the following laboratory criteria:
- Hematologic: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count (PLT) ≥100 × 10⁹/L, hemoglobin (HGB) ≥90 g/L.
- Hepatic: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN) (≤5 × ULN in patients with liver metastases); total serum bilirubin (TBIL) ≤1.5 × ULN; serum albumin ≥30 g/L.
- Renal: serum creatinine (Cr) ≤1.5 × ULN or calculated creatinine clearance ≥50 mL/min using the Cockcroft-Gault formula.
- Coagulation: prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5 × ULN.
- Cardiac: left ventricular ejection fraction (LVEF) ≥50%.
- Negative serum pregnancy test; women of childbearing potential must use a highly effective contraceptive method from study initiation until at least 6 months after the last dose of study medication.
- Voluntary participation with written informed consent obtained prior to any study-related procedures.
Who cannot join
- Cohort A participants must be excluded if any of the following apply:
- Cerebrospinal fluid (CSF) circulation obstruction that cannot be adequately controlled by therapeutic measures.
- MRI evidence of nodular leptomeningeal (LM) disease in the setting of negative CSF cytology.
- Active central nervous system (CNS) infection.
- Clinically significant coagulopathy.
- Cohort B participants must be excluded if leptomeningeal metastasis is documented, defined as either: radiographic evidence of leptomeningeal involvement, or positive CSF cytology, or unequivocal clinical signs or symptoms attributable to leptomeningeal disease.
Show all 14Show fewer
- Presence of clinically significant third-space fluid accumulation (e.g., massive pleural or peritoneal effusion) that cannot be adequately controlled by drainage or other interventions.
- Known hypersensitivity to any study drug or its excipients, or to any prior humanized monoclonal antibody products (e.g., trastuzumab, pertuzumab).
- Prior or current exposure to antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, including but not limited to fam-trastuzumab deruxtecan (DS-8201a).
- Clinically significant cardiovascular disease, including but not limited to: severe or unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association class ≥ II), clinically relevant supraventricular or ventricular arrhythmias requiring therapy or intervention, myocardial infarction within 6 months prior to first study dose, or cerebrovascular accident (including transient ischemic attack).
- Participants known or suspected to interstitial lung disease.
- Concurrent participation in any other interventional drug clinical trial.
- Refusal to comply with protocol-mandated follow-up.
- Presence of any additional severe physical or psychiatric disorder, or any laboratory abnormality that, in the investigator's judgment, could increase the subject's risk, confound study results, or render the patient unsuitable for enrollment.
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
Official title: A Two-cohort Study of SHR-A1811 in the Treatment of HER2-positive Breast Cancer With Brain Metastases, With or Without Leptomeningeal Metastases.
This is a multi-center, open-label, two-cohort study. The purpose of this study is to evaluate the safety, tolerability and efficacy of SHR-A1811 in the treatment of HER2-positive breast cancer with brain and leptomeningeal metastases, and the efficacy and safety of SHR-A1811 in the treatment of HER2-positive breast cancer with brain but without leptomeningeal metastases.
- Conditions
- Breast Cancer, Brain Metastases, Leptomeningeal Metastasis
- Being tested
- SHR-A1811, radiotherapy
- Keywords
- HER2-positive breast cancer, SHR-A1811
- Medical subject headings
- Breast Neoplasms, Brain Neoplasms, Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHR-A1811Drug
Systemic therapy: 4.8 mg/kg administered as an intravenous infusion on Day 1 of each cycle. 3 weeks a cycle. Continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.
SHR-A1811Drug
Intrathecal therapy: Administered intrathecally on Day 1 of each cycle. Dose escalation follows a Bayesian Optimal Interval (BOIN) design with three predefined dose levels-15 mg, 30 mg, and 40 mg. The starting dose level is 15 mg. Patients are enrolled in cohorts of three per dose level. If no dose-limiting toxicities (DLTs) are observed, escalation proceeds to the next higher dose level according to the BOIN algorithm. Treatment is administered for a minimum of two cycles and is continued until cerebrospinal fluid (CSF) cytology achieves negative conversion, completion of six cycles, or intolerable adverse events, whichever occurs first. Extension beyond six cycles may be permitted following investigator's discussion and must be documented with justification.
radiotherapyRadiation
radiotherapy is determined by investigator's choice
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Systemic SHR-A1811 therapy combined with intrathecal SHR-A1811 therapy Receives: Drug: SHR-A1811 |
| Arm 2 | Experimental | Systemic SHR-A1811 therapy combined with radiotherapy Receives: Drug: SHR-A1811; Radiation: radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
1. Number of Dose-Limiting Toxicities (DLTs) in the Sequential Dose-Escalation Cohort
For cohort A. DLT is defined as any of the following events judged by the investigator to be related or possibly related to SHR-A1811 occurring within Cycle 1 (21 days), graded according to NCI-CTCAE v5.0:
- Grade ≥3 neurologic toxicity;
- Any death unless unequivocally attributable to tumor progression or an unrelated exogenous cause.
Measured: Start of treatment until 3-week follow-up
CNS-PFS
For cohort B: Central nervous system- progression free survival: time from the date when the subject first received SHR-A1811 to the first observation of tumor progression of central nervous system or death from any cause.
Measured: Start of treatment until 2-year follow-up
Secondary outcomes (6)
CNS-PFS
For cohort A: Central nervous system- progression free survival: time from the date when the subject first received SHR-A1811 to the first observation of tumor progression of central nervous system or death from any cause.
Measured: Start of treatment until 2-year follow-up
CNS-ORR
For cohort B. Central nervous system- objective response rate: proportion of subjects who achieved complete remission (CR) or partial remission (PR) of central nervous system by primary tumor imaging evaluation.
Measured: Start of treatment until 2-year follow-up
PFS
Progression free survival: time from the date when the subject first received SHR-A1811 to the first observation of tumor progression or death from any cause.
Measured: Start of treatment until 2-year follow-up
OS
Overall survival: time from the date when the subject first received SHR-A1811 to death from any cause.
Measured: Start of treatment until 2-year follow-up
Quality of life score
Evaluated by the quality of life core scale [EORTC QLQ-C30 (Chinese version)] developed by European cancer research and treatment organization. The scope of each domain is 0 to 100. Higher scores in the functional and general health areas indicate better functional status and quality of life, and higher scores in the symptomatic areas indicate more symptoms or problems (poorer quality of life).
Measured: Start of treatment until 2-year follow-up
Incidence and severity of adverse events (AE) and serious adverse events (SAE)
Measured: Start of treatment until 2-year follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2025
- Study start30 Sep 2025 (estimated)
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Beijing Tiantan Hospital
- Responsible party
- Sponsor
- Investigators
- Bin Shao, Principal investigator, Peking University Cancer Hospital & InstituteXiaoyan Li, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07177950
- Sponsor's protocol ID
- MA-BC-II-113
- Status last verified
- Sep 2025
- First submitted
- 2 Sep 2025
- Last updated
- 17 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No