Using PD1 antibody for treating leptomeningeal disease in metastatic solid tumors

Intrathecal Application of PD1 Antibody in Metastatic Solid Tumors With Leptomeningeal Disease (IT-PD1/ NOA 26)

This study is testing if giving a PD1 antibody directly into the spine can help people with leptomeningeal disease from metastatic solid tumors feel better and stay safe.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital Tuebingen (Academic / other)
• Drugs / interventions: nivolumab, Pembrolizumab, Atezolizumab, radiation, prednisone
• Locations: 9 sites (Bonn and 8 other locations)
• Trial ID: NCT05112549 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety of administering PD1 antibody intrathecally to patients with leptomeningeal disease (LMD) associated with metastatic solid tumors. LMD is a severe condition affecting the central nervous system, leading to poor prognosis. The trial will involve patients who have been recommended for intrathecal therapy and will assess the potential benefits of this delivery method compared to traditional intravenous administration. Participants will be monitored for safety and adherence to the study protocol throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of leptomeningeal disease and a Karnofsky performance score greater than 50%.

Not a fit: Patients with severe comorbidities or those who do not meet the eligibility criteria for intrathecal therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with leptomeningeal disease.

How similar studies have performed: While the use of PD1 antibodies has shown efficacy in other settings, the intrathecal application for leptomeningeal disease is a novel approach that has not been extensively tested.

Eligibility criteria

Main Inclusion Criteria:

1. Patient aged ≥ 18 years at the time of signing the informed consent
2. Existing ability to understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
3. Patient is at "good risk" ( NCCN guidelines version 1.2021)
4. Existence of the following Tumor board protocol confirmations: clinical recommendation for intrathecal therapy and evaluation of trial enrolment \& statement on the potential necessity of additional systemic treatment of metastatic tumor outside the CNS
5. Existing ability to adhere to the study visit schedule and other protocol requirements
6. Existing agreement to refrain from donating blood while on study drug and for 30 days after discontinuation from this study treatment
7. Karnofsky performance score \> 50%
8. Diagnosis of LMD by CSF and/or MRI (details see Study protocol)
9. If radiation therapy was performed please confirm: Participants eligible for IT-PD1 should have completed their radiation therapy due to clinical indication \> 2 weeks prior to enrollment into the trial
10. Neurological examination (NANO scale) acc. Nayak et al., 2017 performed
11. MRI assessment at screening is based on the LANO scorecard acc. to Le Rhun et al., 2019
12. Existing ability to undergo intrathecal therapy via an intraventricular catheter (e.g. Ommaya reservoir)
13. Primary tumor tissue for the assessment of PD-1 and PD-L1 is optional at the timepoint of inclusion and enrollment but does need to be shipped before end of the trial.
14. Existing willingness of female patient of childbearing potential and male patient with female partner of childbearing potential to use highly effective contraceptive methods during treatment and for 150 days (male or female, see SmPC) after the last dose (details see Study protocol)

Main Exclusion Criteria:

1. Women during pregnancy and lactation.
2. Previous intrathecal nivolumab application.
3. Patient at "poor risk" (NCCN guidelines version 1.2021)
4. The following differential diagnoses to LMD are exclusion criteria: a. Aseptic, meningitis b. Viral meningitis, c. Bacterial meningitis
5. History of hypersensitivity to monoclonal antibodies
6. Participation in other clinical AMG or MDR trials or observation period of competing trials or if there is otherwise a high risk of insurance law issues intervening between two studies and if the participation affects the primary endpoint of the IT-PD1 study. In case of uncertainty, competing insurances must be contacted prior to participation
7. A clinical condition that in the opinion of the investigator would interfere with the evaluation or interpretation of patient safety or trial results or that would prohibit the understanding of informed consent and compliance with the requirements of the protocol
8. Any treatment-related toxicities from prior systemic anti-tumor or immune therapy not having resolved to CTCAE version 5.0 grade 1, with the exception of alopecia
9. Patient with confirmed history of current autoimmune disease
10. Patients with any disease resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy
11. Existence of clinically significant active infection (details see study protocol)
12. Inability to undergo MRI with contrast agent
13. The underlying primary tumor has not a registered and authorized indication in the European Union for intravenous treatment with Nivolumab, Pembrolizumab or Atezolizumab (details see study protocol). In addition, leptomeningeal disease of solid tumors with a high tumor mutational burden is also eligible.
14. Existence of abnormal laboratory values for the following values in hematology, coagulation parameters, liver and renal function (details see study protocol)
15. Patients who have received live or attenuated vaccine therapy used for prevention of infectious disease within 4 weeks of the first IT application of nivolumab
16. Patients requiring chronic systemic corticosteroid therapy (\> 10 mg prednisone or equivalent per day) or any other immunosuppressive therapies (including anti-TNF-a therapies)

Where this trial is running

Bonn and 8 other locations

• Universitätsklinikum Bonn — Bonn, Germany (Recruiting)
• University Hospital Freiburg, Neurosurgery — Freiburg im Breisgau, Germany (Recruiting)
• University Hospital Heidelberg, Neurooncology — Heidelberg, Germany (Not_yet_recruiting)
• SLK-Kliniken Heilbronn GmbH Klinik — Heilbronn, Germany (Recruiting)
• University Hospital Mannheim, Neurology Clinic — Mannheim, Germany (Recruiting)
• Klinikum rechts der Isar/Technische Universität München — München, Germany (Recruiting)
• Katharinenhospital Stuttgart — Stuttgart, Germany (Recruiting)
• University Hospital Tübingen, Neurooncology — Tübingen, Germany (Recruiting)
• University Hospital Ulm, ECTU - Early Clinical Trail Unit — Ulm, Germany (Recruiting)

Study contacts

• Study coordinator: Ghazaleh Tabatabai, Prof.Dr.

Conditions Leptomeningeal Disease