Laser Interstitial Thermotherapy (LITT) Combined With Checkpoint Inhibitor for Recurrent GBM (RGBM)

Primary Objectives: 1. Phase I: To determine the optimal timing for combining LITT and pembrolizumab in patients with rGBM: • To determine the feasibility, safety, tolerability and side effect profiles for combining LITT and pembrolizumab at various time points pre-LITT vs. post-LITT (Phase I). 2. Phase II: To estimate the response to pembrolizumab combined with LITT in patients with rGBM; • To estimate the response rate after treatment with LITT combined with pembrolizumab in patients with rGBM (Phase II). 3. To collect and record the side effect profiles for combining LITT and pembrolizumab (Phase I and Phase II). Secondary Objectives: 1. To determine the effect of pembrolizumab on systemic immune microenvironment in patients with rGBM. 2. To determine the effect of pembrolizumab on the intra-tumoral immunosuppressive microenvironment within rGBM. 3. Secondary for Phase II, to estimate progression free survival (PFS) and overall survival (OS) after treatment with LITT combined with pembrolizumab in patients with rGBM (Phase II). 4. Measure radiological response using both conventional RANO criterion, a modified RANO (RANOi) designed specifically for immunotherapy response assessment, as well as MRI fingerprinting (MRF), recently demonstrated by the PI and collaborators to accurately and precisely distinguish recurrent GBM from radiation injury. 5. Correlate clinical and radiological response to known biomarkers of GBM such as Isocitrate Dehydrogenase 1 (IDH-1) mutations, Isocitrate Dehydrogenase 2 (IDH-2) mutations, Methyl-Guanine Methyl Transferase (MGMT) promoter methylation, Phosphatase and tensin homologue (PTEN) loss and KI-67. Study Design: The Phase I component will involve up to two of a possible 3 cohorts of 3-4 patients each for a total of 6-8 evaluable patients. Each patient will undergo a stereotactic biopsy. If GBM or Gliosarcoma is confirmed by frozen section, patients will undergo LITT then treatment with 200 mg pembrolizumab IV. Cohort I will receive pembrolizumab on post operative day 14 and every 3 weeks thereafter. In the event that one patient suffers non-hematologic toxicity of grade 3 or more, or if hematologic toxicity is grade 4 or higher, the investigators will delay the 2nd dose of pembrolizumab by 3 weeks and a 4th patient will be accrued. If there are two patients in the initial cohort with non-hematologic toxicities grade 3, or if hematological toxicity in two patients is grade 4 or higher, the second cohort will delay initiation of pembrolizumab until post operative day 35 after LITT. Conversely, if there are no non-hematologic adverse events (AEs) of grade 3 or higher, the investigators will proceed to cohort IB using the same dose of pembrolizumab given 7 days prior to surgery, then every 3 weeks. Similarly, feasibility and safety will be addressed as above in deciding whether or not to proceed to the next cohort. The Phase II component of the study will consist of additional patients receiving pembrolizumab at the earliest tolerated time post LITT: * 14 days post-op * -7 days pre-op; * 35 days post-opto achieve a total of 23 evaluable patients at the earliest tolerated dose.