Pembrolizumab in Patients With Leptomeningeal Disease

Inclusion Criteria: 1. Willing and able to provide written informed consent for the trial. 2. 18 years of age on day of signing informed consent. 3. Histologically or cytologically confirmed solid tumor malignancy. 4. Cytologically confirmed LMD or radiologically detectable LMD defined as either/or: A measurable lesion on contrast-enhanced MRI of either the Brain or Total Spine greater than 3mm that has not been radiated within the last 3 months prior to commencement of study therapy. Positive cerebrospinal fluid (CSF) cytology 5. Patients may be newly diagnosed or have received any number of lines of prior anti cancer therapy. However, patients are required to have received available therapies for their primary disease, as deemed appropriate by the treating investigator. 6. Non escalating steroid requirement at the time of consent and study drug initiation for the treatment of central nervous system (CNS) symptoms. 7. Local radiation therapy (RT) is allowed as needed to manage symptoms appropriately, as long as there remains a measurable lesion in the CNS. 8. Whole brain RT may be used, without a pre-defined washout period, prior to commencement of study therapy if the lesion that has been radiated is not the sole measurable lesion, or the patient is eligible based on positive CSF cytology. 9. Patients may continue therapy with a targeted agent if CNS disease developed while receiving the agent, and for defined regimens that have been deemed safe when combined with anti PD 1 therapy. 10. Be willing to provide tissue from an archival tissue specimen in selected patients, where available. 11. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. 12. Demonstrate adequate organ function as defined in Table 3, all screening labs should be performed within 10 days of treatment initiation. Table 3. 13. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 14. Female subjects of childbearing potential (Section 4.8.2) must be willing to use an adequate method of contraception as outlined in Section 4.8.2 Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. 15. Male subjects of childbearing potential (Section 4.8.2) must agree to use an adequate method of contraception as outlined in Section 4.8.2 Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Exclusion Criteria: 1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks or 5 half lives of the first dose of treatment, whichever is shorter. 2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 3. Has a known history of active Bacillus Tuberculosis (TB) 4. Hypersensitivity to pembrolizumab or any of its excipients. 5. Has had a prior anti cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 6. Has had prior chemotherapy, targeted small molecule therapy other than pre specified allowed agents detailed in section 4.2.6, or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 7. All major surgery including prior surgery to the brain within 3 weeks of commencement of study therapy. 8. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. 9. Subjects with previously treated brain metastases may participate provided they are not using escalating steroids for brain metastases at the time of trial consent and study drug initiation, and there remains a measurable lesion in the CNS, as per section 4.2.6. 10. Has 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. 11. Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis. 12. Has an active infection requiring systemic therapy. 13. Prior disease progression on anti-PD-1 therapy 14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 16. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (HCV) (e.g., HCV RNA \[qualitative\] is detected). 19. Has received a live vaccine within 30 days of planned start of study therapy. 20. Contraindication to MRI. 21. Patients with a condition related to their cancer or leptomeningeal disease requiring urgent intervention that has not been clinically managed or stabilized prior to the time of consent. 22. Brain metastases with risk of mass effect that would contraindicate lumbar puncture, as detailed in section 6.1.2.8.3. 23. Live vaccines within 30 days prior to the first dose of trial treatment. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.