Clinical trial · Interventional
Phase I/II Study of Intrathecal/Ommaya T-DXd in HER2-Expressing Breast Cancer With Leptomeningeal/Brain Metastases
Evaluating Safety and Efficacy of INtrathecal or Ommaya ReserVoir Administration of T-DXd in Patients With HER2-Expressing Breast Cancer With Active Leptomeningeal and/or Brain Metastases Based on Systemic Therapy: Phase I/II Study
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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 therapies improve survival, intracranial disease control remains limited due to poor BBB penetration. Preclinical data show no detectable T-DXd/DXd in CSF, though intrathecal trastuzumab demonstrates preliminary safety/efficacy in HER2+ LM. This study evaluates intrathecal/intra-Ommaya T-DXd plus systemic therapy in active HER2+ meningeal/brain metastases, assessing safety, intracranial efficacy, and CSF/peripheral blood T-DXd distribution to clarify BBB penetration potential. Findings may guide novel therapeutic strategies for this high-need population.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Cancer | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| T-DXd | Drug | Trastuzumab Deruxtecan | ALIAS |
Design
Arms and outcomes
Arms (10)
- type
- EXPERIMENTAL
- label
- Phase I/Arm A(Intrathecal Dose-Escalation Phase)
- description
- Population : T-DXd-naïve subjects with leptomeningeal metastases (LM), with or without concurrent brain metastases (BM). Cycle 1 : Intrathecal (IT) T-DXd monotherapy to assess cerebrospinal fluid (CSF) and systemic pharmacokinetics (PK). Cycles 2+ : IT T-DXd combined with intravenous (IV) T-DXd in a dose-escalation design to determine the maximum tolerated dose (MTD) . DLT Evaluation : The first two cycles serve as the dose-limiting toxicity (DLT) observation window . Endpoint : The recommended Phase 2 dose (RP2D) will be determined by investigator assessment
- interventionNames
- Drug: T-DXd
- type
- EXPERIMENTAL
- label
- Phase I/Arm B(Systemic-to-Intrathecal Transition Phase)
- description
- Population : T-DXd-naïve subjects with LM ± BM. Cycle 1 : IV T-DXd monotherapy to characterize CSF and systemic PK profiles. Cycles 2+ : IT administration of the RP2D of T-DXd combined with IV therapy
- interventionNames
- Drug: T-DXd
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * 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 Criteria: * 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.
References
Publications (0)
Data not yet available