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

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 documentprior 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: clinicalrecommendation for intrathecal therapy and evaluation of trial enrolment & statementon the potential necessity of additional systemic treatment of metastatic tumoroutside the CNS

5. Existing ability to adhere to the study visit schedule and other protocolrequirements

6. Existing agreement to refrain from donating blood while on study drug and for 30days 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-PD1should have completed their radiation therapy due to clinical indication > 2 weeksprior 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 thetimepoint of inclusion and enrollment but does need to be shipped before end of thetrial.

14. Existing willingness of female patient of childbearing potential and male patientwith female partner of childbearing potential to use highly effective contraceptivemethods during treatment and for 150 days (male or female, see SmPC) after the lastdose (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 competingtrials or if there is otherwise a high risk of insurance law issues interveningbetween two studies and if the participation affects the primary endpoint of theIT-PD1 study. In case of uncertainty, competing insurances must be contacted priorto participation

7. A clinical condition that in the opinion of the investigator would interfere withthe evaluation or interpretation of patient safety or trial results or that wouldprohibit the understanding of informed consent and compliance with the requirementsof the protocol

8. Any treatment-related toxicities from prior systemic anti-tumor or immune therapynot 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 requiringpermanent 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 theEuropean Union for intravenous treatment with Nivolumab, Pembrolizumab orAtezolizumab (details see study protocol). In addition, leptomeningeal disease ofsolid 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 ofinfectious disease within 4 weeks of the first IT application of nivolumab

16. Patients requiring chronic systemic corticosteroid therapy (> 10 mg prednisone orequivalent per day) or any other immunosuppressive therapies (including anti-TNF-atherapies)