A Two-cohort Study of SHR-A1811 in the Treatment of HER2-positive Breast Cancer With Brain Metastases

Get Involved

A Two-cohort Study of SHR-A1811 in the Treatment of HER2-positive Breast Cancer With Brain Metastases

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 75 Years
Gender	Female

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Women aged 18-75 years (inclusive). 2. Histologically or cytologically confirmed HER2-positive advanced breast cancer (IHC 3+, or IHC 2+ with ISH amplification). 3. 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.

4. Anticipated life expectancy >12 weeks. 5. ECOG performance status 0-2. 6. Adequate organ function as defined by the following laboratory criteria: 1. Hematologic: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count (PLT) ≥100 × 10⁹/L, hemoglobin (HGB) ≥90 g/L. 2. 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. 3. Renal: serum creatinine (Cr) ≤1.5 × ULN or calculated creatinine clearance ≥50 mL/min using the Cockcroft-Gault formula. 4. Coagulation: prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5 × ULN. 5. Cardiac: left ventricular ejection fraction (LVEF) ≥50%. 7. 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. 8. Voluntary participation with written informed consent obtained prior to any study-related procedures.

Exclusion Criteria:

1. Cohort A participants must be excluded if any of the following apply: 1. Cerebrospinal fluid (CSF) circulation obstruction that cannot be adequately controlled by therapeutic measures. 2. MRI evidence of nodular leptomeningeal (LM) disease in the setting of negative CSF cytology. 3. Active central nervous system (CNS) infection. 4. Clinically significant coagulopathy. 2. 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. 3. 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. 4. Known hypersensitivity to any study drug or its excipients, or to any prior humanized monoclonal antibody products (e.g., trastuzumab, pertuzumab). 5. Prior or current exposure to antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, including but not limited to fam-trastuzumab deruxtecan (DS-8201a). 6. 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). 7. Participants known or suspected to interstitial lung disease. 8. Concurrent participation in any other interventional drug clinical trial. 9. Refusal to comply with protocol-mandated follow-up. 10. 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 Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT07177950
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Peking University Cancer Hospital & Institute
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Bin ShaoXiaoyan Li
Principal Investigator Affiliation	Peking University Cancer Hospital & InstituteBeijing Tiantan Hospital
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Breast Cancer, Brain Metastases, Leptomeningeal Metastasis

Arms & Interventions

Arms

Experimental: Arm 1

Systemic SHR-A1811 therapy combined with intrathecal SHR-A1811 therapy

Experimental: Arm 2

Systemic SHR-A1811 therapy combined with radiotherapy

Interventions

Drug: - SHR-A1811

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.

Drug: - SHR-A1811

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.

Radiation: - radiotherapy

radiotherapy is determined by investigator's choice