Leptomeningeal MetastasisPhase 1IT-IONCT05598853
Intrathecal Double Checkpoint Inhibition
A Phase 1 study testing intrathecal nivolumab and intrathecal ipilimumab in people with Leptomeningeal Metastasis and Non-small Cell Lung Cancer Stage IV, run by University of Zurich at 3 sites in Switzerland.
Trial summary
The objective of the present study is to determine the feasibility and to explore anti-tumor activity of intrathecal double immune checkpoint inhibition for patients with newly diagnosed leptomeningeal metastases from non-small cell lung cancer without driver mutation or melanoma. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Leptomeningeal Metastasis, Non-small Cell Lung Cancer Stage IV, Melanoma Stage IV
- What is being tested?
- intrathecal nivolumab and intrathecal ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesSwitzerland
- Study dates
- 25 Nov 2022to Dec 2025
- Phase
- Phase 1
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed confirmed or probable leptomeningeal metastases according to European Association of Neuro-Oncology (EANO) - European Society for Medical oncology (ESMO) criteria (Le Rhun et al., 2017).
- Histologically confirmed (from primary tumor or from a metastatic lesion, including in the brain) non-small cell lung cancer without actionable oncogenic driver mutation or melanoma. Programmed death-ligand 1 (PD-L1) expression status (from primary tumor or from a metastatic lesion, including brain) is optional, but should be documented if available
- Requirements for patients with non-small cell lung cancer: non-small cell lung cancer without a specified targetable oncogenic driver alteration: sensitising Epidermal Growth Factor Receptor (EGFR) mutation (exon 19-del and 21-L858R), anaplastic lymphoma kinase (ALK) or ROS proto-oncogene-1 (ROS1) rearrangement.
- Clinically eligible for systemic immunotherapy with nivolumab and ipilimumab at the time of enrolment as judged by the investigator. If already initiated, the systemic treatment must be well tolerated, without common terminology criteria for adverse events (CTCAE) grade 3 or more toxicity, and there must be no evidence of systemic progression and no indication for whole brain radiotherapy. Intrathecal immunotherapy alone may be acceptable for exceptional patients after discussion with the coordinators of the study. Systemic immunotherapy can be started later in these patients based on investigator decision.
- Patients previously treated with systemic chemotherapy must have received the last dose at least 21 days prior to treatment initiation, patients who have received another investigational agent must have received the last treatment at least 14 days prior to treatment initiation.
- Age of 18 years or older on day of signing informed consent, female or male.
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- Karnofsky performance status of 60 or more.
- Life expectancy >8 weeks. Patients with rapidly progressive systemic disease are not eligible.
- Patients may receive steroids to control symptoms related to central nervous system involvement, but the dose must be stable or decreasing and < 4 mg per 24 hours of dexamethasone (or equivalent) in the last 7 days. Patients should experience stability of neurological symptoms for at least 7 days. Physiologic replacement doses of steroids are permitted.
- Cerebrospinal MRI criteria (on the baseline MRI, performed within 14 days prior to study treatment initiation)
- MRI can be normal or can show leptomeningeal metastases, including nodules <0.5 cm diameter largest diameter (or more if stereotactic radiosurgery is planned)
- No evidence of cerebrospinal fluid flow obstruction at the discretion of the investigator
- Co-existing asymptomatic brain metastases <2 cm diameter are permitted. Larger asymptomatic or oligosymptomatic brain metastases are permitted if they are planned to be treated by stereotactic radiosurgery
- Central nervous system radiotherapy criteria:
- Focal brain radiotherapy by stereotactic radiotherapy is allowed for meningeal nodules > 5 mm diameter or concomitant brain metastases. The treated lesions cannot be used as a target for the evaluation of the study treatment
- Prior brain focal radiotherapy for central nervous system metastases is permitted if completed at least 14 days prior to enrolment, but the treated lesions cannot be used as a target for the evaluation of the study treatment
- Planned whole brain radiotherapy is not allowed
- Prior whole brain radiotherapy for brain metastases is permitted if terminated at least 3 months prior enrolment.
- Planned or prior craniospinal irradiation is not allowed
- Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test within 24 hours before the first dose of study treatment.
- Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
- Written informed consent for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention.
Who cannot join
- Leptomeningeal metastases related to primary tumors other than non-small cell lung cancer without driver mutation or melanoma.
- Inability to undergo craniospinal MRI evaluation.
- Progressive parenchymal brain metastases thought to require whole brain radiotherapy.
- Contra-indication to lumbar puncture or to implantation of a ventricular device.
- Prior intrathecal chemotherapy, intrathecal immunotherapy or intrathecal targeted therapy.
- Ventriculo-peritoneal shunt (except if intrathecal therapy is administered via a ventricular device with an ON/OFF option).
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- Condition requiring systemic treatment with either corticosteroids (> 4 mg daily dexamethasone equivalents) or other immunosuppressive medications within 7 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Patients with a history of pneumonitis or previous non-hematological grade >2 toxicity under previous immunotherapy treatment.
- Active infection (systemic or central nervous system) within 7 days prior to initiation of the study drug.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or active chronic infection.
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) even if fully immunocompetent on antiretroviral therapy due to the unknown effects of HIV on the immune response to combined nivolumab plus ipilimumab or the unique toxicity spectrum of these drugs in patients with HIV infection.
- Use of vaccines containing live virus for prevention of infectious disease within 12 weeks prior to study drug.
- History of allergy to study drug components and history of severe hypersensitivity reaction to any monoclonal antibody.
- Concurrent treatment with other systemic cancer-derived pharmacotherapies is not allowed. No other concomitant intrathecal therapy is allowed.
- Any investigational anticancer therapy other than those under investigation in this study.
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
- Intention to become pregnant during the course of the study. Women who are pregnant.
- Women who are breast feeding and who do not agree to discontinue nursing prior to the first study treatment and for the period defined in the protocol.
- Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study.
Trial locations and contacts
3 sites in 1 country.
Switzerland3 sites
University Hospital Basel
Basel
University Hospital Geneva
Geneva
University Hospital Zurich
Zurich, Canton of Zurich
About this study
Official title: Intrathecal Administration of Anti-PD1/Anti-CTLA-4 in Combination With Systemic Combination of Anti-PD1/Anti-CTLA-4 in Patients With NSCLC Without Oncogenic Driver Mutation or Melanoma and Newly Diagnosed Leptomeningeal Metastasis: a Multicentric Phase I Study
The objective of the present study is to determine the feasibility and to explore anti-tumor activity of intrathecal double immune checkpoint inhibition for patients with newly diagnosed leptomeningeal metastases from non-small cell lung cancer without driver mutation or melanoma.
Read the detailed description
The treatment regimen within the IT-IO study consists of intrathecal administration of nivolumab/ipilimumab in combination with systemic combined nivolumab/ipilimumab.
The scheme of administration of systemic nivolumab/ipilimumab corresponds to the current standard of care for non-small cell lung cancer and for melanoma patients.
- Being tested
- intrathecal nivolumab and intrathecal ipilimumab
- Keywords
- intrathecal, immunotherapy
- Medical subject headings
- Meningeal Carcinomatosis, Carcinoma, Non-Small-Cell Lung, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intrathecal nivolumab and intrathecal ipilimumabDrug
Patients shall be treated with a fixed dose of intrathecal nivolumab and increasing doses of intrathecal ipilimumab. From cycle 2, patients will receive systemic nivolumab/ipilimumab in addition to intrathecal treatment. Systemic nivolumab/ipilimumab corresponds to the current standard of care for non-small cell lung cancer and for melanoma patients.
| Study group | Role | What they receive |
|---|---|---|
| Intrathecal nivolumab and intrathecal ipilimumab | Experimental | The experimental treatment will be combined from cycle 2 with systemic nivolumab and systemic ipilimumab Receives: Drug: intrathecal nivolumab and intrathecal ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose of intrathecal (IT) nivolumab/ipilimumab followed by IT nivolumab/ipilimumab plus systemic nivolumab/ipilimumab
Determination of the maximum tolerated dose or the recommended phase II dose for combined intrathecal immunotherapy
Measured: 3 weeks
Secondary outcomes (5)
steroid intake
steroid intake in mg dexamethasone at each assessment
Measured: through study completion, an average of 1 year
compartmental efficacy (PFS) of nivolumab/ipilimumab combined with systemic nivolumab/ipilimumab
progression free survival in months by compartments level (leptomeningeal compartment, brain compartment, central nervous system compartment, extra-central nervous system compartment, overall compartment)
Measured: through study completion, an average of 1 year
compartmental efficacy (response) of nivolumab/ipilimumab combined with systemic nivolumab/ipilimumab
response rate in percentage by compartments level (leptomeningeal compartment, brain compartment, central nervous system compartment, extra-central nervous system compartment, overall compartment)
Measured: through study completion, an average of 1 year
efficacy of nivolumab/ipilimumab combined with systemic nivolumab/ipilimumab
overall survival in months
Measured: through study completion, an average of 1 year
prognostic factors
association between survival and prognostic factors. The list of items to analyze will be determined prior to the analysis to consider potential new data available in the literature. The analysis will be performed in the whole population, per cerebrospinal fluid cytology assessment at diagnosis (positive cerebrospinal fluid cytology versus equivocal or negative cerebrospinal fluid cytology); per tumor entity (non-small cell lung cancer versus melanoma)
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2022
- Study start25 Nov 2022
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leptomeningeal MetastasisStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05598853
- Sponsor's protocol ID
- IT-IO (CA209-6K7)
- Acronym
- IT-IO
- Status last verified
- Sep 2025
- First submitted
- 11 Oct 2022
- Last updated
- 2 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intrathecal Administration of Anti-PD1/Anti-CTLA-4 in Combination With Systemic Combination of Anti-PD1/Anti-CTLA-4 in Patients With NSCLC Without Oncogenic Driver Mutation or Melanoma and Newly Diagnosed Leptomeningeal Metastasis: a Multicentric Phase I Study
- ClinicalTrials.gov ID
- NCT05598853
- Acronym / sponsor ID
- IT-IO / IT-IO (CA209-6K7)
- Keywords
- intrathecal, immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 25 Nov 2022 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 28 Oct 2022 (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.
The objective of the present study is to determine the feasibility and to explore anti-tumor activity of intrathecal double immune checkpoint inhibition for patients with newly diagnosed leptomeningeal metastases from non-small cell lung cancer without driver mutation or melanoma.
Detailed description
The treatment regimen within the IT-IO study consists of intrathecal administration of nivolumab/ipilimumab in combination with systemic combined nivolumab/ipilimumab.
The scheme of administration of systemic nivolumab/ipilimumab corresponds to the current standard of care for non-small cell lung cancer and for melanoma patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intrathecal nivolumab and intrathecal ipilimumab | Experimental | Drug: intrathecal nivolumab and intrathecal ipilimumabThe experimental treatment will be combined from cycle 2 with systemic nivolumab and systemic ipilimumab |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Newly diagnosed confirmed or probable leptomeningeal metastases according to European Association of Neuro-Oncology (EANO) - European Society for Medical oncology (ESMO) criteria (Le Rhun et al., 2017).
- Histologically confirmed (from primary tumor or from a metastatic lesion, including in the brain) non-small cell lung cancer without actionable oncogenic driver mutation or melanoma. Programmed death-ligand 1 (PD-L1) expression status (from primary tumor or from a metastatic lesion, including brain) is optional, but should be documented if available
- Clinically eligible for systemic immunotherapy with nivolumab and ipilimumab at the time of enrolment as judged by the investigator. If already initiated, the systemic treatment must be well tolerated, without common terminology criteria for adverse events (CTCAE) grade 3 or more toxicity, and there must be no evidence of systemic progression and no indication for whole brain radiotherapy. Intrathecal immunotherapy alone may be acceptable for exceptional patients after discussion with the coordinators of the study. Systemic immunotherapy can be started later in these patients based on investigator decision.
- Patients previously treated with systemic chemotherapy must have received the last dose at least 21 days prior to treatment initiation, patients who have received another investigational agent must have received the last treatment at least 14 days prior to treatment initiation.
- Age of 18 years or older on day of signing informed consent, female or male.
Key exclusion criteria (20 listed)
- Leptomeningeal metastases related to primary tumors other than non-small cell lung cancer without driver mutation or melanoma.
- Inability to undergo craniospinal MRI evaluation.
- Progressive parenchymal brain metastases thought to require whole brain radiotherapy.
- Contra-indication to lumbar puncture or to implantation of a ventricular device.
- Prior intrathecal chemotherapy, intrathecal immunotherapy or intrathecal targeted therapy.
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 nivolumab and intrathecal ipilimumabPatients shall be treated with a fixed dose of intrathecal nivolumab and increasing doses of intrathecal ipilimumab. From cycle 2, patients will receive systemic nivolumab/ipilimumab in addition to intrathecal treatment. Systemic nivolumab/ipilimumab corresponds to the current standard of care for non-small cell lung cancer and for melanoma patients. | Drug | Intrathecal nivolumab and intrathecal ipilimumab |
Primary outcome
Recommended phase II dose of intrathecal (IT) nivolumab/ipilimumab followed by IT nivolumab/ipilimumab plus systemic nivolumab/ipilimumab
Time frame: 3 weeks
Determination of the maximum tolerated dose or the recommended phase II dose for combined intrathecal immunotherapy
5 secondary outcomes
steroid intake
Time frame: through study completion, an average of 1 year
compartmental efficacy (PFS) of nivolumab/ipilimumab combined with systemic nivolumab/ipilimumab
Time frame: through study completion, an average of 1 year
compartmental efficacy (response) of nivolumab/ipilimumab combined with systemic nivolumab/ipilimumab
Time frame: through study completion, an average of 1 year
efficacy of nivolumab/ipilimumab combined with systemic nivolumab/ipilimumab
Time frame: through study completion, an average of 1 year
prognostic factors
Time frame: through study completion, an average of 1 year
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 2 Oct 2025.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing intrathecal nivolumab and intrathecal ipilimumab in people with Leptomeningeal Metastasis and Non-small Cell Lung Cancer Stage IV, run by University of Zurich at 3 sites in Switzerland.
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 22 inclusion and 20 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: under way, not looking for participants, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Switzerland. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase II dose of intrathecal (IT) nivolumab/ipilimumab followed by IT nivolumab/ipilimumab plus systemic nivolumab/ipilimumab (time frame: 3 weeks). 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 2 Oct 2025.