Study of Pembrolizumab and M032 (NSC 733972)

Inclusion Criteria: Phase I/Cohort I: Participants are eligible to be included in the study only if all of the following criteria apply: Patients must have histologically or cytologically confirmed glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma, and is deemed a potential candidate for resection of the recurrent tumor. Prior therapy: Patients must have failed external beam radio-therapy to the brain, and if eligible and tolerated, undergone appropriate treatment with temozolomide chemotherapy. All radiation and additional chemotherapies must have been completed at least 4 weeks prior to enrollment. Prior therapy with nitrosoureas must have been completed at least 6 weeks prior to enrollment. Phase I/Cohort II or Phase II: Participants are eligible to be included in the study only if all of the following criteria apply: Patient must have MRI findings consistent with probable malignant glioma, have no previous diagnosis of glioma, and have had either no history of any surgery for brain tumor. The exception to this requirement is that patients who have under-gone biopsy for diagnosis only and have not received any other treatment. All patients must be potential candidates for resection of the probably malignant glioma tumor. Should a patient in Phase I/Cohort II or Phase II be found on final pathologic diagnosis to not have a glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma, he/she will receive no other doses of M032 other than that administered at the time of craniotomy, nor will he/she receive any doses of Pembrolizumab. He/she will be followed for evidence of toxicity of M032 only and will be considered off-study for all efficacy and other secondary endpoints. All patients, whether in Phase I/Cohort II or Phase II shall also be required to meet the following eligibility and be subject to the exclusion criteria below: 1. Age ≥18 years. Because no dosing or adverse event data are currently available on the use of M032 in patients \<16 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials. 2. Karnofsky Performance Status (KPS) ≥70% (see Appendix B). 3. Life expectancy of greater than 4 weeks. 4. Preoperatively, the lesion must be ≥1.0 cm in diameter as determined by MRI. 5. The effects of M032 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for six months after receiving the final dose of M032. Because it is currently unknown if M032 can be transmitted by sexual contact, a barrier method of birth control must be employed and for six (6) months following the administration of the last dose of this study drug. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. Subjects should also refrain from donating blood during the trial. 6. Ability to understand and the willingness to sign a written informed con-sent document. 7. Females of childbearing potential must not be pregnant; this will be con-firmed by a negative serum pregnancy test within 14 days prior to starting study treatment. 8. Patients must have normal organ and marrow function as defined below: 1. leukocytes……………………. \>3,000/μl 2. absolute neutrophil count………. \>1,500/μl 3. platelets…………………………... \>100,000/μl 4. total bilirubin……………………. within normal institutional limits 5. AST(SGOT)/ALT(SGPT)………… \<2.5 X institutional upper limit of normal creatinine within normal institutional limits Or 6. creatinine clearance……………... \>60 mL/min/1.73 m2 for patients with creatinine levels above insti-tutional normal Exclusion Criteria: A Woman of Child Bearing Potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to allocation.(see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Has received prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137). Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation. Note: Participants must have recovered from all adverse events (AEs) due to previous thera-pies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Is currently participating in or has participated in a study of an interventionally-directed investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent or if the agent is directed at analysis and not treatment (e.g., certain PET tracers, etc.). Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 2 mg daily of dexamethasone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Has a known additional malignancy that is prog