Status:

RECRUITING

Phase I/II Study of Intrathecal/Ommaya T-DXd in HER2-Expressing Breast Cancer With Leptomeningeal/Brain Metastases

Lead Sponsor:

Fudan University

Conditions:

Breast Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief Summary

Multiple trials confirm systemic T-DXd efficacy in HER2+ breast cancer with leptomeningeal/brain metastases, yet median LM survival remains 3-4 months, highlighting unmet needs. While systemic therapi...

Detailed Description

Multiple clinical trials have demonstrated the efficacy of systemic T-DXd in advanced HER2-expressing breast cancer with leptomeningeal and/or brain metastases. However, the median survival of leptome...

Eligibility Criteria

Inclusion

  • Age ≥18 years, regardless of gender.
  • HER2-expressing advanced or metastatic breast cancer
  • Leptomeningeal metastasis
  • Subjects with active brain metastases only must have at least one intracranially measurable lesion (RANO-BM criteria).
  • Adequate organ and bone marrow function
  • No radiotherapy, chemotherapy, targeted therapy, immunotherapy, endocrine therapy, or surgery within 2 weeks prior to enrollment (or within 5 half-lives of prior therapy, whichever is shorter).
  • All prior treatment-related toxicities must have resolved to ≤Grade 1

Exclusion

  • Diagnosis of other malignancies within the past 5 years, except for cured carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin, other in situ carcinomas, or papillary thyroid carcinoma.
  • Uncontrolled concurrent illnesses including, but not limited to: persistent or active infections, uncontrolled or clinically significant cardiovascular diseases, severe chronic gastrointestinal disorders with diarrhea, or psychiatric/social conditions that may compromise compliance with study requirements, significantly increase AE risks, or impair the subject's ability to provide written informed consent.
  • History of (non-infectious) ILD/non-infectious pneumonitis requiring steroid therapy, current ILD/non-infectious pneumonitis, or suspected ILD/non-infectious pneumonitis that cannot be ruled out by imaging during screening.
  • Clinically significant pulmonary comorbidities
  • Use of immunosuppressants or systemic corticosteroids (\>10 mg/day prednisone equivalent) for immunosuppression within 2 weeks prior to first dose (excluding intranasal/inhaled corticosteroids).
  • Any active autoimmune disease or history of autoimmune disease with potential recurrence.
  • Uncontrolled infections requiring IV antibiotics, antivirals, or antifungals.
  • Active primary immunodeficiency, known HIV infection, active HBV (HBsAg+ with HBV DNA ≥500 IU/mL) or HCV infection. HCV antibody-positive subjects are eligible only if PCR confirms HCV RNA negativity.
  • Radiographic evidence of tumor encasement/invasion of major blood vessels, or investigator-determined high risk of fatal hemorrhage due to probable vascular invasion during treatment.
  • Pregnant/lactating women, or subjects of reproductive potential unwilling/unable to use effective contraception.
  • Any other condition deemed by investigators to potentially affect trial conduct or outcome interpretation.

Key Trial Info

Start Date :

April 18 2025

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

February 28 2027

Estimated Enrollment :

139 Patients enrolled

Trial Details

Trial ID

NCT07134153

Start Date

April 18 2025

End Date

February 28 2027

Last Update

August 21 2025

Active Locations (2)

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Page 1 of 1 (2 locations)

1

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China, 200032

2

Fudan University Shanghai Cancer Cancer

Shanghai, Shanghai Municipality, China, 200043