Sacituzumab Govitecan for the Treatment of Recurrent Glioblastoma

Inclusion Criteria

• At least 18 years of age
• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator’s Institutional Review Board (IRB)/Ethics Committee
• Histologically confirmed IDH wild-type (primary) GBM. Molecular GBM (as per The Consortium to Inform Molecular and Practical Approaches to Central Nervous System Tumor Taxonomy-Not Official World Health Organization [cIMPACT-NOW] 3) is allowed as is gliosarcoma and epithelioid glioblastoma. IDH­-mutant glioma is not allowed
• Progression following standard combined modality treatment with radiation and temozolomide chemotherapy if O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylated * Prior temozolomide is not required for MGMT unmethylated, but patient must have received standard doses of radiation * Inclusion of additional investigational therapy, including maintenance therapy, with standard frontline therapy is not exclusionary. No additional lines of therapy given for disease that has recurred are allowed * Prior tumor-treating field therapy is not excluded, nor considered and additional line of therapy as this is often given concurrently with other therapy lines
• Patients may have had been operated for recurrence, but if operated must have had surgery a minimum of 2 weeks prior to enrollment and have a magnetic resonance imaging (MRI) completed within 48 hours following surgery
• No radiotherapy within the 3 months prior to the diagnosis of progression
• Willingness to forego tumor-treatment field (Optune) therapy during participation in the study
• Stable or decreasing dosage of steroids for 7 days prior to the baseline MRI scan
• Recovered from toxicities of prior therapy to grade 0 or 1, except for neuropathy (grade =< 2) and alopecia
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy of at least 6 months
• Bilirubin =< 1.5 times upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 times upper limit of normal (ULN)
• Creatinine clearance >= 30 mL/minute according to the Cockcroft and Gault formula
• Absolute neutrophil count (ANC) >= 1500 cells/uL
• Platelet count >= 100,000/uL
• Hemoglobin >= 9.0 g/dL
• All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an intrauterine device [IUD]) with their partner from entry into the study through 6 months after the last dose
• Availability of biological material for central review and biomarker evaluation
• Untreated recurrent or residual disease that is measurable by RANO criteria at time of enrollment. Multifocal and infratentorial disease is allowed
• Positive Trop-2 expression (H-Score ≥ 200), as verified by central review at University of Texas Health San Antonio (UTHSA)

Exclusion Criteria

• Prior treatment with bevacizumab or other VEGF inhibitors or VEGF-receptor signaling inhibitors
• The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug
• The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible
• The subject is unable to undergo MRI scan (e.g., has pacemaker)
• The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (e.g., carbamazepine, phenytoin, phenobarbital, primidone)
• The subject is pregnant or breast-feeding
• The subject has serious intercurrent illness, such as: * Hypertension (two or more blood pressure [BP] readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment * Non-healing wound, ulcer, or bone fracture * Significant cardiac arrhythmias * Untreated hypothyroidism * Unhealed rectal or peri-rectal abscess * Uncontrolled active infection * Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug * Any history of cardiac arrhythmia or heart block * Stroke or transient ischemic attack within 6 months
• The subject has received any of the following prior anticancer therapy: * Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed. Rhenium nanoliposomes are also allowed as our institution has experience with the imaging interpretation and management of this therapy * Systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (e.g., tamoxifen) within 7 days or 5 half-lives, whichever is shorter, prior first dose of study drug * Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug * Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug * Prior treatment with carmustine wafers
• Patients with radiographically or clinically apparent leptomeningeal involvement are excluded
• Patients with known diagnosis of chronic obstructive pulmonary disease (COPD), body mass index (BMI) ≥ 40, neuromuscular disease (including amyotrophic lateral sclerosis [ALS]) or bicarb ≥ 30 are excluded from participation in the oxygen enhanced (OE)-magnetic resonance imaging (MRI) but may be enrolled on the study provided they otherwise meet all criteria
• Patients who are, in the opinion of investigator, unable or suitable to complete trial requirements or at excessive risk from trial participation