LITT and Pembrolizumab in Recurrent Brain Metastasis

INCLUSION CRITERIA 1. Histologic confirmation of primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor 2. At least one metastatic lesion has had prior SRS. Each patient's scan must be reviewed by a neurosurgeon or radiation oncologist prior to enrollment. 3. KPS ≥ 70. 4. 18 years or older. 5. Adequate bone marrow and organ function as defined below: 1. ANC ≥ 1,500/mcL 2. Platelets ≥ 100,000/mcL 3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (transfusion is allowed) 4. Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine \> 1.5 x IULN 5. Serum total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total bilirubin i) 1.5 x IULN f) AST (SGOT) and ALT (SGPT) ≤ 3 x IULN 6. Candidate for pembrolizumab treatment. 7. Candidate for LITT treatment: 1. Metastatic lesions individually measuring 3.5 cm or less 2. Only lesions that are growing or new will be treated with LITT 3. Five (5) or less target metastatic lesions that are new or growing 4. Lesions accessible with a laser probe as determined by the neurosurgeon performing the procedure 5. Patient able to undergo MRI scans (no incompatible MRI hardware, etc.) 8. A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively, within 30 days prior to study enrollment. 9. Participants of childbearing age must use effective contraception: a) Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. Refer to Section 9.3 for guidance on highly effective contraceptive methods. i) WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or oophorectomy) or who is not post-menopausal. Post-menopause is defined as: (1) Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or (2) For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL. b) Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug. 10\. Ability of the patient to understand and willingness to sign an IRB approved written informed consent document. 11\. Steroid dose equivalent to dexamethasone dose of ≤ 6mg daily at the time of enrollment. EXCLUSION CRITERIA 1. Actively participating in another clinical trial on active study treatment; follow-up or observational status is acceptable if more than 2 weeks since last study treatment. 2. History of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (with the exception of daily dexamethasone ≤ 6 mg). 3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that will no resolve prior to delivery of treatment (LITT), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements. 4. History of active autoimmune disease requiring systemic treatment within 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. (Note that prior autoimmune diseases at Grade 1 or 2 per CTCAE v. 4.0 - in the last 2 years that were deemed related to prior use of immunotherapy, will be allowed under this protocol, provided that continuation or subsequent resumption of immunotherapy, regardless of whether systemic treatment had been given, did not result in worsening of signs and symptoms of the aforementioned autoimmune diseases). 5. Pneumonitis within the past 3 years (Note that patients with a history of pneumonitis in the past 3 years that was not aggravated by immunotherapy including immune checkpoint inhibitors or that has clinically resolved or improved and has not recurred or progressed clinically with subsequent immunotherapy including immune checkpoint inhibitors are eligible to participate in the study). 6. Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test at screening. 7. Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 24 weeks after the last dose of study drug. 8. Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA \[qualitative\] is detected) infection. 9. Known history of active TB (bacillus tuberculosis). 10. Known history of HIV (HIV 1/2 antibodies).