Trial of Anti-Tim-3 in Combination With Anti-PD-1 and SRS in Recurrent GBM

Exclusion Criteria

• •1. History of other malignancy, unless the patient has been disease-free for at ≥5 years. Curatively treated basal or squamous cell carcinoma of the skin, totally excised melanoma of stage IIA or lower, low or intermediate-grade localized prostate cancer (Gleason sum ≤7), and curatively-treated carcinoma in situ of the cervix, breast, or bladder are allowed regardless.
• •2. Any known metastatic extracranial or leptomeningeal disease.
• •3. Evidence of acute intracranial / intra-tumoral hemorrhage
• •4. History of organ or hematopoietic stem cell (HSC) transplant
• •5. Receiving greater than 4 mg dexamethasone/day (or equivalent amount of an alternative corticosteroid) for a minimum of 5 days prior to screening visit. Subjects with an autoimmune condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study entry \*NOTE: Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone or equivalent, are permitted in the absence of active autoimmune disease
• •6. Prior treatment with immune-modulating therapy, other than steroids.
• •7. Pregnant or nursing (lactating) women
• •8. Known positive history of HIV, active Hepatitis B, and/or active Hepatitis C infection.
• •9. Subjects with active, or recent history of known or suspected autoimmune disease. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• •10. Major surgery, outside of a craniotomy/resection, within 2 weeks of the first dose of study treatment (mediastinoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery).
• •11. Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within 4 weeks of initiation of study treatment
• •12. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
• •13. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
• •14. History of evidence upon physical/neurological examination of other central nervous system condition (i.e. seizures, abscess) unrelated to cancer, unless adequately controlled by medication or considered not potentially interfering with protocol treatment.
• •15. History of allergy or hypersensitivity to study drug components.
• •16. Prisoners or subjects who are involuntarily incarcerated.
• •17. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infections disease) illness.