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

NCT07177950 | Not Yet Recruiting Phase 1

• 1 other identifier: MA-BC-II-113
• Study Type: interventional
• Target: 51
• Locations: 0 countries
• Sites: N/A

Brief 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 cancer with brain but without leptomeningeal metastases.

Conditions

Breast Cancer; Brain Metastases; Leptomeningeal Metastasis

Keywords

HER2-positive breast cancer; SHR-A1811

Outcome Measures

Primary Outcomes (2)

• 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: 1. Grade ≥3 neurologic toxicity; 2. Any death unless unequivocally attributable to tumor progression or an unrelated exogenous cause.

  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.

  Start of treatment until 2-year follow-up

Secondary Outcomes (6)

• CNS-PFS

  Start of treatment until 2-year follow-up

• CNS-ORR

  Start of treatment until 2-year follow-up

• PFS

  Start of treatment until 2-year follow-up

• OS

  Start of treatment until 2-year follow-up

• Quality of life score

  Start of treatment until 2-year follow-up

Study Arms (2)

Arm 1

EXPERIMENTAL

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

Drug: SHR-A1811

Arm 2

EXPERIMENTAL

Systemic SHR-A1811 therapy combined with radiotherapy

Drug: SHR-A1811; Radiation: radiotherapy

Interventions

SHR-A1811 DRUG

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.

Arm 1; Arm 2

radiotherapy RADIATION

radiotherapy is determined by investigator's choice

Arm 2

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead
• Beijing Tiantan Hospital: collaborator

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms; Meningeal Carcinomatosis

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Meningeal Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Bin Shao

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

• Xiaoyan Li

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bin Shao

CONTACT

+86-010-88196380; shaobin79@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: September 17, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2029
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share