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

NCT07134153 · tracked via the Priya Life Science China tracker

Sponsor

Fudan University

Phase

Phase 1/2

Started

2025-05-12

Last updated

2026-10-26

Condition(s) studied

Breast Cancer

Investigational drug(s) / intervention(s)

T-DXd →

T-DXd: 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

Study 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 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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

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.

Primary outcome measure(s)

Phase I Stage Cohort A: Maximum Tolerated Dose (MTD) — Up to 21 days after the first dose
Cohort A: Maximum Tolerated Dose (MTD) of intracapsular administration，In the dose increment stage, the highest dose whose estimated DLT rate is closest to the target DLT rate but does not exceed the upper bound of the equivalent interval of DLT rate is selected as MTD.
Phase I Stage Cohort B: Maximum serum concentration (Cmax) — Up to 21 days after the first dose
Cohort B: Maximum serum concentration (Cmax) of T-DXd in cerebrospinal fluid and blood will be investigated.
Phase I Stage Cohort B:Time to maximum serum concentration (Tmax) — Up to 21 days after the first dose
Cohort B: Time to maximum serum concentration (Tmax) of T-DXd in cerebrospinal fluid and blood will be investigated.
Phase I Stage Cohort B:Half-life (T1/2) — Up to 21 days after the first dose
Cohort B: Half-life (T1/2) of T-DXd in cerebrospinal fluid and blood will be investigated.
Phase II Stage Cohorts A: LM-OS — 18 months
Cohorts A: leptomeningeal metastasis-overall survival（LM-OS）
Phase II Stage Cohorts B: LM-OS — 18 months
Cohorts B: leptomeningeal metastasis-overall survival（LM-OS）
Phase II Stage Cohorts C: LM-ORR — 18 months
Cohorts C: leptomeningeal metastasis-Objective Response Rate（LM-ORR）
Phase II Stage Cohorts D: LM-ORR — 18 months
Cohorts D: leptomeningeal metastasis-Objective Response Rate（LM-ORR）
Phase II Stage Cohorts E: LM-OS — 18 months
Cohorts E: leptomeningeal metastasis-overall survival（LM-OS）
Phase II Stage Cohorts F: LM-OS — 18 months
Cohorts F: leptomeningeal metastasis-overall survival（LM-OS）
Phase II Stage Cohorts G: LM-ORR — 18 months
Cohorts G: leptomeningeal metastasis-Objective Response Rate（LM-ORR）
Phase II Stage Cohorts H: LM-ORR — 18 months
Cohorts H: leptomeningeal metastasis-Objective Response Rate（LM-ORR）

Trial sites (2)

Facility	City	Region	Status
Fudan University Shanghai Cancer Center	Shanghai	Shanghai Municipality	Recruiting
Fudan University Shanghai Cancer Cancer	Shanghai	Shanghai Municipality	Recruiting

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07134153 on ClinicalTrials.gov ↗ ← All trials in China