Leptomeningeal MetastasesPhase 2ITST-ADC-LMNCT07833657
Combined Intrathecal and Systemic Therapy With Trastuzumab Rezetecan for Leptomeningeal Metastases
A Phase 2 study testing Intrathecal and systemic administration of Trastuzumab Rezetecan in people with Leptomeningeal Metastases and Solid Tumors, run by Jiuda Zhao at 1 site in China.
Trial summary
This phase II clinical study enrolls patients with leptomeningeal metastases from solid tumors. Participants will receive intrathecal and systemic administration of Trastuzumab Rezetecan. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leptomeningeal Metastases, Solid Tumors
- What is being tested?
- Intrathecal and systemic administration of Trastuzumab Rezetecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteChina
- Study dates
- Sep 2026to Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥ 18 years of any gender; histologically confirmed solid tumor; signed informed consent form.
- Patients with Type I LMD (defined as positive cerebrospinal fluid cytology or positive leptomeningeal biopsy) or Type II LMD (diagnosed based on clinical manifestations and neuroimaging alone) according to the European Association of Neuro-Oncology (EANO)-European Society for Medical Oncology (ESMO) clinical practice guidelines;patients with treatment-naive LMD or recurrent LMD after radiotherapy.
- Investigators assess that immediate radiotherapy for leptomeningeal lesions is not required, or the patient declines radiotherapy.
- Expected survival ≥ 6 weeks.
- Left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiogram; adequate organ and bone marrow function.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-4.
- All enrolled subjects will be stratified into 2 predefined cohorts based on tumor HER2 status: Cohort 1: Patients with leptomeningeal disease secondary to solid tumors without HER2 protein overexpression and without HER2-activating mutations; Cohort 2: Patients with leptomeningeal disease secondary to solid tumors with HER2 protein overexpression or harboring HER2-activating mutations.
Who cannot join
- Presence of severe central nervous system (CNS) complications, such as progressive cerebral edema; recurrent seizures refractory to standardized antiepileptic therapy. Note: "refractory recurrent seizures" refers to persistent clinical seizures despite adequate standardized antiepileptic treatment. Subjects with a prior history of epilepsy with long-term seizure control on medication are not excluded by this criterion.
- Receipt of whole-brain radiotherapy or other intrathecal therapies within the recent 4 weeks, which may interfere with efficacy assessment.
- History of active interstitial lung disease (ILD) or pneumonia.
- Concurrent severe systemic diseases, including but not limited to:
- 4.1 Active autoimmune disease or CNS infection; 4.2 Active infections (e.g., pulmonary tuberculosis, active hepatitis B, HIV infection); 4.3 Moderate to severe hepatic or renal dysfunction (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3 × ULN, creatinine clearance (CrCl) < 30 ml/min); 4.4 Uncontrolled heart failure, severe arrhythmia or hypertension; 4.5 Known inherited or acquired bleeding/thrombotic tendency (e.g., hemophilia, coagulopathy, thrombocytopenia); and/or coagulation disorders (international normalized ratio (INR) > 2.0, prothrombin time (PT) > 16 s) with bleeding risk, or receiving thrombolysis or anticoagulant treatment.
- History of allergy or hypersensitivity to the study drug or its components.
- Major surgery or severe traumatic injury within 28 days prior to enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Phase II, Prospective, Multicenter, Two-Cohort Study of Combined Intrathecal and Systemic Therapy With Trastuzumab Rezetecan in Patients With Leptomeningeal Metastases From Solid Tumors
This phase II clinical study enrolls patients with leptomeningeal metastases from solid tumors. Participants will receive intrathecal and systemic administration of Trastuzumab Rezetecan. The study aims to obtain clinical evidence about the efficacy and safety of this antibody-drug conjugate (ADC) given via intrathecal plus systemic routes. It hopes to offer a new treatment option for these patients with hard-to-manage disease and provide scientific support for optimizing treatment strategies for solid tumor patients with leptomeningeal metastases.
Read the detailed description
This is a prospective, multicenter, single-arm, dual-cohort phase II clinical trial. It is designed to evaluate the efficacy and safety of combined intravenous and intrathecal Trastuzumab Rezetecan in adult patients with leptomeningeal metastases (LMD) from solid tumors.Participants are stratified into two cohorts based on HER2 expression and mutation status. All enrolled patients receive dualroute treatment with intravenous plus intrathecal Trastuzumab Rezetecan. The systemic intravenous dose is 4.8 mg/kg administered every 3 weeks, with a 21-day treatment cycle. The intrathecal dose is set at 20% of the single systemic dose. In terms of administration schedule, intrathecal injection is performed once weekly during Cycle 1 and Cycle 2, and once per treatment cycle starting from Cycle 3.The primary endpoint is the 3-month overall survival (OS) rate. Secondary endpoints cover intracranial tumor response and survival outcomes, cerebrospinal fluid tumor cell clearance rate, and extracranial tumor response. This study also evaluates treatment-related adverse events according to NCI-CTCAE v5.0 and assesses patients' quality of life using the EORTC QLQ-C30 questionnaire.
- Conditions
- Leptomeningeal Metastases, Solid Tumors
- Being tested
- Intrathecal and systemic administration of Trastuzumab Rezetecan
- Keywords
- leptomeningeal metastases, solid tumors, Trastuzumab-rezetecan, intrathecal administration, antibody-drug conjugate
- Medical subject headings
- Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrathecal and systemic administration of Trastuzumab RezetecanDrug
Trastuzumab-rezetecan is administered via combined intrathecal and systemic routes. Systemic dosing: 4.8 mg/kg by intravenous infusion once every 3 weeks (q3w). Intrathecal dosing: 20% of the systemic dose, administered once weekly during Cycle 1 and Cycle 2, then once every 3 weeks from Cycle 3 onward.
| Study group | Role | What they receive |
|---|---|---|
| HER2 status | Experimental | All enrolled participants receive intrathecal plus systemic administration of Trastuzumab Rezetecan. Subjects are stratified into two predefined cohorts based on HER2 status. Cohort 1: Patients with leptomeningeal disease (LMD) from solid tumors without HER2 positivity or HER2 mutations.Cohort 2: Patients with leptomeningeal disease (LMD) secondary to solid tumors with HER2 protein overexpression or HER2-activating mutations Receives: Drug: Intrathecal and systemic administration of Trastuzumab Rezetecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-month Overall Survival Rate
3-month overall survival (OS) rate is defined as the percentage of all enrolled participants who are still alive at 3-months from the date of receiving study treatment.
Measured: 3-months from the date of receiving study treatment
Secondary outcomes (7)
Leptomeningeal Metastasis-Progression-Free Survival (LM-PFS)
Time from treatment initiation to the first documentation of leptomeningeal metastasis progression (based on neurological examination, cerebrospinal fluid testing, or neuraxis MRI) or death from any cause, whichever occurs first, in patients with solid tumor-associated leptomeningeal metastasis receiving intrathecal plus intravenous Trastuzumab Rezetecan.
Measured: From treatment initiation until disease progression, death, or study discontinuation, assessed up to 18 months.
Leptomeningeal Metastasis-Objective Response Rate (LM-ORR)
LM-ORR corresponds to Best Overall Response. It is not a single time-point assessment, but the best leptomeningeal metastasis therapeutic response documented from treatment initiation up to disease progression, study discontinuation, death, or pre-specified maximum follow-up.
Measured: From treatment initiation until disease progression, death, or study discontinuation, assessed up to 18 months.
Cerebrospinal Fluid Cytology Conversion Rate
For intrathecal treatment: Trastuzumab rezetecan is administered intrathecally once weekly in Cycle 1 and Cycle 2; starting from Cycle 3 and thereafter, intrathecal Trastuzumab rezetecan is given once per 3-week cycle. The cerebrospinal fluid cytology conversion rate is preliminarily evaluated after 6-week intrathecal treatment. Sustained absence of tumor cells in cerebrospinal fluid at this time point is defined as cerebrospinal fluid conversion to negative. The cerebrospinal fluid cytology conversion rate is calculated as: (Number of patients with negative cerebrospinal fluid tumor cells at 6-week post-treatment ÷ Total number of treated patients with leptomeningeal metastasis) × 100%
Measured: 6 weeks after initiation of intrathecal study treatment
Extracranial Objective Response Rate (EC-ORR)
EC-ORR is defined as the percentage of patients whose best overall response of extracranial lesions is complete response (CR) or partial response (PR). Tumor assessments are performed per RECIST version 1.1from the date of first study treatment until study discontinuation secondary to disease progression.
Measured: From treatment initiation until disease progression, death, or study discontinuation, assessed up to 18 months.
Leptomeningeal Metastasis-Second Progression-Free Survival (LM-PFS2)
The measurement time of PFS2 is from the date of first disease progression to the date of second disease progression or death. LM-PFS2 is defined as the time from the first leptomeningeal metastasis progression to second leptomeningeal metastasis progression or death from any cause, whichever occurs first. Patients without the above-mentioned events will be censored at the date of last valid follow-up.
Measured: From the date of first leptomeningeal metastasis progression until second leptomeningeal metastasis progression, death, or study discontinuation, assessed up to 18 months.
Adverse events (AEs)
Number of subjects with treatment-related adverse events, which will be assessed and graded according to NCI-CTCAE version 5.0 criteria.
Measured: From treatment initiation until 30-day safety follow-up after last study drug administration, assessed up to 18 months.
Changes in the dimensions of the EORTC QLQ-C30 scale
Physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, and global health status before and after treatment. EORTC QLQ-C30 scores range from 0 to 100. Higher scores represent better quality of life.
Measured: FFrom treatment initiation up to 21 days after the last treatment cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2026
- Study startSep 2026 (estimated)
- Primary completionJun 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiuda Zhao
- Sponsor type
- University, hospital or other
- Collaborators
- The First Affiliated Hospital of Lanzhou Medical University, Xi'an International Medical Center Hospital, Shandong Cancer Hospital and Institute
- Responsible party
- Sponsor-investigator, Jiuda Zhao, Affiliated Hospital of Qinghai University
- Investigators
- JiuDa Zhao, Principal investigator, Affiliated Hospital of Qinghai University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07833657
- Sponsor's protocol ID
- 2026LLPJ-012
- Acronym
- ITST-ADC-LM
- Status last verified
- Sep 2026
- First submitted
- 8 Sep 2026
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared publicly. This is an investigator-initiated single-arm phase II trial. Restrictions from institutional ethics requirements, patient-related privacy protection regulations, and limited dedicated data-sharing resources prevent public release of de-identified individual-level participant data. Aggregated summary study results will be published in peer-reviewed journals.
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Prospective, Multicenter, Two-Cohort Study of Combined Intrathecal and Systemic Therapy With Trastuzumab Rezetecan in Patients With Leptomeningeal Metastases From Solid Tumors
- ClinicalTrials.gov ID
- NCT07833657
- Acronym / sponsor ID
- ITST-ADC-LM / 2026LLPJ-012
- Conditions
- Leptomeningeal Metastases, Solid Tumors
- Keywords
- leptomeningeal metastases, solid tumors, Trastuzumab-rezetecan, intrathecal administration, antibody-drug conjugate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Jiuda ZhaoUniversity, hospital or other
- Collaborators
- The First Affiliated Hospital of Lanzhou Medical University, Xi'an International Medical Center Hospital, Shandong Cancer Hospital and Institute
- Study start
- Sep 2026 (estimated)
- Primary completion
- Jun 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 22 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II clinical study enrolls patients with leptomeningeal metastases from solid tumors. Participants will receive intrathecal and systemic administration of Trastuzumab Rezetecan. The study aims to obtain clinical evidence about the efficacy and safety of this antibody-drug conjugate (ADC) given via intrathecal plus systemic routes. It hopes to offer a new treatment option for these patients with hard-to-manage disease and provide scientific support for optimizing treatment strategies for solid tumor patients with leptomeningeal metastases.
Detailed description
This is a prospective, multicenter, single-arm, dual-cohort phase II clinical trial. It is designed to evaluate the efficacy and safety of combined intravenous and intrathecal Trastuzumab Rezetecan in adult patients with leptomeningeal metastases (LMD) from solid tumors.Participants are stratified into two cohorts based on HER2 expression and mutation status. All enrolled patients receive dualroute treatment with intravenous plus intrathecal Trastuzumab Rezetecan. The systemic intravenous dose is 4.8 mg/kg administered every 3 weeks, with a 21-day treatment cycle. The intrathecal dose is set at 20% of the single systemic dose. In terms of administration schedule, intrathecal injection is performed once weekly during Cycle 1 and Cycle 2, and once per treatment cycle starting from Cycle 3.The primary endpoint is the 3-month overall survival (OS) rate. Secondary endpoints cover intracranial tumor response and survival outcomes, cerebrospinal fluid tumor cell clearance rate, and extracranial tumor response. This study also evaluates treatment-related adverse events according to NCI-CTCAE v5.0 and assesses patients' quality of life using the EORTC QLQ-C30 questionnaire.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HER2 status | Experimental | Drug: Intrathecal and systemic administration of Trastuzumab RezetecanAll enrolled participants receive intrathecal plus systemic administration of Trastuzumab Rezetecan. Subjects are stratified into two predefined cohorts based on HER2 status. Cohort 1: Patients with leptomeningeal disease (LMD) from solid tumors without HER2 positivity or HER2 mutations.Cohort 2: Patients with leptomeningeal disease (LMD) secondary to solid tumors with HER2 protein overexpression or HER2-activating mutations |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged ≥ 18 years of any gender; histologically confirmed solid tumor; signed informed consent form.
- Patients with Type I LMD (defined as positive cerebrospinal fluid cytology or positive leptomeningeal biopsy) or Type II LMD (diagnosed based on clinical manifestations and neuroimaging alone) according to the European Association of Neuro-Oncology (EANO)-European Society for Medical Oncology (ESMO) clinical practice guidelines;patients with treatment-naive LMD or recurrent LMD after radiotherapy.
- Investigators assess that immediate radiotherapy for leptomeningeal lesions is not required, or the patient declines radiotherapy.
- Expected survival ≥ 6 weeks.
- Left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiogram; adequate organ and bone marrow function.
Key exclusion criteria (7 listed)
- Presence of severe central nervous system (CNS) complications, such as progressive cerebral edema; recurrent seizures refractory to standardized antiepileptic therapy. Note: "refractory recurrent seizures" refers to persistent clinical seizures despite adequate standardized antiepileptic treatment. Subjects with a prior history of epilepsy with long-term seizure control on medication are not excluded by this criterion.
- Receipt of whole-brain radiotherapy or other intrathecal therapies within the recent 4 weeks, which may interfere with efficacy assessment.
- History of active interstitial lung disease (ILD) or pneumonia.
- Concurrent severe systemic diseases, including but not limited to:
- 4.1 Active autoimmune disease or CNS infection; 4.2 Active infections (e.g., pulmonary tuberculosis, active hepatitis B, HIV infection); 4.3 Moderate to severe hepatic or renal dysfunction (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3 × ULN, creatinine clearance (CrCl) < 30 ml/min); 4.4 Uncontrolled heart failure, severe arrhythmia or hypertension; 4.5 Known inherited or acquired bleeding/thrombotic tendency (e.g., hemophilia, coagulopathy, thrombocytopenia); and/or coagulation disorders (international normalized ratio (INR) > 2.0, prothrombin time (PT) > 16 s) with bleeding risk, or receiving thrombolysis or anticoagulant treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intrathecal and systemic administration of Trastuzumab RezetecanTrastuzumab-rezetecan is administered via combined intrathecal and systemic routes. Systemic dosing: 4.8 mg/kg by intravenous infusion once every 3 weeks (q3w). Intrathecal dosing: 20% of the systemic dose, administered once weekly during Cycle 1 and Cycle 2, then once every 3 weeks from Cycle 3 onward. | Drug | HER2 status |
Primary outcome
3-month Overall Survival Rate
Time frame: 3-months from the date of receiving study treatment
3-month overall survival (OS) rate is defined as the percentage of all enrolled participants who are still alive at 3-months from the date of receiving study treatment.
7 secondary outcomes
Leptomeningeal Metastasis-Progression-Free Survival (LM-PFS)
Time frame: From treatment initiation until disease progression, death, or study discontinuation, assessed up to 18 months.
Leptomeningeal Metastasis-Objective Response Rate (LM-ORR)
Time frame: From treatment initiation until disease progression, death, or study discontinuation, assessed up to 18 months.
Cerebrospinal Fluid Cytology Conversion Rate
Time frame: 6 weeks after initiation of intrathecal study treatment
Extracranial Objective Response Rate (EC-ORR)
Time frame: From treatment initiation until disease progression, death, or study discontinuation, assessed up to 18 months.
Leptomeningeal Metastasis-Second Progression-Free Survival (LM-PFS2)
Time frame: From the date of first leptomeningeal metastasis progression until second leptomeningeal metastasis progression, death, or study discontinuation, assessed up to 18 months.
Adverse events (AEs)
Time frame: From treatment initiation until 30-day safety follow-up after last study drug administration, assessed up to 18 months.
Changes in the dimensions of the EORTC QLQ-C30 scale
Time frame: FFrom treatment initiation up to 21 days after the last treatment cycle
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared publicly. This is an investigator-initiated single-arm phase II trial. Restrictions from institutional ethics requirements, patient-related privacy protection regulations, and limited dedicated data-sharing resources prevent public release of de-identified individual-level participant data. Aggregated summary study results will be published in peer-reviewed journals.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
JiuDa Zhao principal investigator
Affiliated Hospital of Qinghai University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intrathecal and systemic administration of Trastuzumab Rezetecan in people with Leptomeningeal Metastases and Solid Tumors, run by Jiuda Zhao at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact JiuDa Zhao, Dr (+86-971-3921561, jiudazhao@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-month Overall Survival Rate (time frame: 3-months from the date of receiving study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.