• 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 IRB/Ethics Committee.

• Histologically confirmed IDH wild type (primary) GBM. Molecular GBM (as per 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-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 with standard frontline therapy is not exclusionary. No additional lines of therapy given for recurrent disease.

⁃ 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 an 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.

⁃ ECOG performance status ≤ 2.

⁃ Life expectancy of at least 6 months.

⁃ Acceptable liver function:

∙ Bilirubin ≤ 1.5 times upper limit of normal

‣ AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN)

⁃ Acceptable renal function:

⁃ • Creatinine clearance ≥30 mL/minute according to the Cockcroft and Gault formula

⁃ Acceptable hematologic status (without hematologic support):

∙ 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 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 Science Center at San Antonio (UTHSA).