Study of Icapamespib (PU-AD) in Patients With Recurrent Malignant Glioma

Inclusion Criteria: * Male or female subjects having histologically confirmed IDH wildtype glioblastoma (Parts 1 and 2), or grade 3 or 4 IDH mutant astrocytoma (Part 1 only) per WHO criteria * Subjects must be at 1st, 2nd, or 3rd recurrence (Part 1) or 1st or 2nd recurrence (Part 2) and with at least 5 subjects clinically requiring reoperation for tumor progression (Part 2). ; Note: recurrence is defined as progression following initial therapy (i.e., radiation, chemotherapy, or radiation + chemotherapy); if the participant had a surgical resection for relapsed disease and no anti-tumor therapy instituted for up to 12 weeks, this is considered one recurrence. * Measurable disease as defined by modified RANO (1 cm × 1 cm minimum dimensions, at least 12 weeks after final radiotherapy dose; if new disease is outside radiotherapy field, \<4 weeks is acceptable). * Cranial MRI performed within 14 days prior to study entry. * Age equal to or greater than 18 years * Karnofsky performance status of \>60 at screening * Adequate bone marrow, liver and renal functions (tests must be performed within 14 days prior to enrollment).The following laboratory values must be documented within 3 days prior to the first dose of study drug Absolute neutrophil count (ANC) ≥1.5 × 109/L Platelet count ≥100 × 109/L Estimated creatinine clearance (CrCl) \>60 mL/min by Cockcroft-Gault formulation Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 × the upper limit of normal (ULN) Total bilirubin ≤1.5 × ULN (unless due to Gilbert's syndrome) Serum albumin ≥2.8 g/dL International normalized ratio (INR) \<1.5 (except subjects maintained on anticoagulant medications) * Negative serum or urine pregnancy test (females of childbearing potential only). * Willingness to follow highly effective means of contraception * Able and willing to give informed consent Exclusion Criteria: * Currently receiving any concomitant anti-cancer medication * Prior treatment with Gliadel wafers. * No radiation within 4 weeks of starting treatment. * Has tumor localized primarily to the brainstem or spinal cord. * A history of any other primary malignancy that has not been treated with curative intent and that has not been in complete remission for at least 2 years (exempt from the two year limit are non-melanoma skin cancer and cervical carcinoma in-situ on biopsy or a squamous intraepithelial lesion on PAP smear). * Active infection requiring systemic treatment. * Any significant medical illnesses or toxicities that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy. Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism, e.g. congestive heart failure, moderate to severe liver and renal disease, other cancers. * History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV) or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening * QT interval corrected with the Fridericia formula (QTcF) on average of triplicate ECG readings (taken approximately 5 minutes apart) at Screening Visit ECG or Baseline Visit ECGs \>450 msec for males or \>470 msec for females (except when QT prolongation is associated with right or left bundle branch block, in which case enrollment is allowed). * Has active ocular condition unrelated to primary intracranial pathology, that in the opinion of the investigator, may alter visual acuity during the course of the study. * The need for concomitant use of long-acting gastric pH elevating agents (proton pump inhibitors or H2-receptor antagonists) at study entry and during the study (note: gastric locally-acting antacids may be allowed if administered \>2 hours before or after dosing). * The need for concomitant use of any drugs that are sensitive substrates of CYP 450 isozymes with narrow therapeutic index for at least 7 days prior to administration of the first dose of IMP and throughout the study. * The need for concomitant use of any drugs that are strong inhibitors or inducers of cytochrome (CYP) 450 isozymes at least 7 days prior to administration of the first dose of IMP and throughout the study. * Has taken other investigational drugs or participated in any clinical study within 30 days or 5 half-lives (if known) of the investigational drug, whichever is longer, prior to first dose of IMP in this study; or is currently participating in another clinical study. * Has taken corticosteroids at greater than dexamethasone 4 mg daily or equivalent daily, participants taking \<4 mg daily are eligible if the dose has been stable for ≥ 1 week before the first dose of study drug. * Other unspecified reasons that, in the opinion of the investigator or Samus and/or its delegated medical monitor, place the subject at risk or make the subject unsuitable for the study or unable or unwilling to comply with the requirements of the study * History or presence of conditions, which in the judgment of the investigator, are known to interfere with the absorption distribution, metabolism or excretion of drugs, such as prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy) * Prior exposure to icapamespib or other Hsp90 inhibitors