Accelerated Checkpoint Therapy for Any Steroid Dependent Patient With Brain Metastases

Inclusion Criteria:

1. Patients with the following histologically confirmed diagnoses will be eligible forenrolment: malignant melanoma, non-small cell lung cancer and renal cell carcinomaand genitourinary carcinoma not-otherwise specified.

2. At the time of enrolment patients must have central nervous system metastasesrequiring corticosteroid therapy and have already started corticosteroid therapy.

3. Patients eligible for treatment with an available, standard-of-care immunecheckpoint inhibitor regimen.

4. Patients with extracranial disease will be eligible for enrolment, however thepresence of extracranial measurable disease is not a requirement for enrolment.

5. Patients must be 18 years of age or older.

6. Patients must be capable of providing consent to enrolment and willing to complywith study treatment and follow-up.

7. Patients with a performance status of ECOG 0-2 will be eligible for enrolment.

8. Measurable intracranial disease must be present according to RECIST 1.1 criteria.

9. Patients with hyperthyroidism or hypothyroidism but that are stable on hormonereplacement will not be excluded.

10. Women of child bearing potential (WOCBP) must have a negative serum (or urine)pregnancy test within 72 hours prior to the first dose of study treatment. WOCBP isdefined as any female who has experienced menarche and who has not undergonesurgical sterilization (hysterectomy or bilateral oophorectomy or bilateralsalpingectomy) and is not postmenopausal. Menopause is defined as 12 months ofamenorrhea in a woman over age 45 years in the absence of other biological orphysiological causes.

11. Patients of childbearing / reproductive potential should use adequate birth controlmethods, as defined by the investigator, during the study treatment period and for aperiod of 30 days after the last dose of study drug.

12. Absence of any condition hampering compliance with the study protocol and follow- upschedule; those conditions should be discussed with the patient before registrationin the trial.

13. The following adequate organ function laboratory values must be met:

Hematological:

• Absolute neutrophil count (ANC) >1.0

• Platelet count >100

• Hemoglobin >90 mg/dL

Renal:

• Serum creatinine <2x ULN

Hepatic:

• Total serum bilirubin <1.5x ULN

• AST and ALT <3x ULN

Coagulation:

• International Normalized Ratio (INR) <1.5x ULN (unless patient is receivinganticoagulant therapy as long as PT or PTT is within therapeutic range of intendeduse of anticoagulants)

• Activated Partial Thromboplastin Time (aPTT) <1.5x ULN (unless patient is receivinganticoagulant therapy as long as PT or PTT is within therapeutic range of intendeduse of anticoagulants)

Exclusion Criteria:

1. Known history of human immunodeficiency virus (HIV), active Hepatitis B or HepatitisC. Testing for HIV, HBV or HCV is not mandatory for enrolment to study, but mayoccur at the discretion of the investigator.

2. Active autoimmune disease that has required systemic treatment in past 2 years (i.e.with use of disease modifying agents, corticosteroids or immunosuppressive drugs).Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroidreplacement therapy for adrenal or pituitary insufficiency, etc.) is not considereda form of systemic treatment.

3. Patients receiving non-steroid immunosuppressive agents (examples may includeanti-TNF biologic agents, methotrexate, mycophenylate mofetil, tacrolimus) will beexcluded from this study.

4. Known prior severe hypersensitivity to study drugs or any component in itsformulations.