LUMINOS-101: Lerapolturev (PVSRIPO) and Pembrolizumab in Patients With Recurrent Glioblastoma

Inclusion Criteria

• ≥ 18 years of age.
• Recurrent supratentorial glioblastoma (GBM) confirmed via prior histology by the site's neuropathologist or designate.
• Histologically confirmed recurrent glioblastoma (rGBM) within 6 weeks of Lerapolturev infusion will not require a biopsy to confirm active tumor prior to catheter placement
• Progression of primary glioblastoma or transformation from a lower grade to a higher grade is acceptable for recurrence and as for primary glioblastoma, must be confirmed via prior histology by site pathologist
• Enhancing lesion ≥1 cm shortest diameter to ≤ 5.5 cm longest diameter in all planes.
• Before catheter placement based on screening MRI and at the time of catheter placement via CT prior to infusion, neurosurgical investigator must confirm placement of infusion catheter within or through the progressive enhancing tumor is feasible and at a safe distance relative to eloquent brain function, with the tip of the catheter being placed:
• Within the enhancing portion or in the vicinity of enhancement of target lesion (ie, infiltrative disease).
• ≥ 0.5 cm from ventricles.
• ≥ 1 cm deep into the brain.
• ≥ 0.5 cm from corpus callosum.
• First or second relapse supported by MRI or CT scan; relapse is defined as progression following initial/prior therapy(ies).
• Failed previous first line therapy: maximum surgical resection and radiotherapy (RT) (plus concomitant chemotherapy followed by maintenance chemotherapy if unknown or methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter). Patients who begin but do not complete chemotherapy/RT may still be considered for eligibility at the discretion of Sponsor.
• Karnofsky Performance Status ≥ 70 at screening and baseline.
• Undergone prior vaccination against PV and received a boost immunization with trivalent inactivated poliovirus vaccine (IPOL®) at least 1 week, but less than 6 weeks, prior to administration of Lerapolturev. Note: Patients who are unsure of their prior vaccination status/who have not been vaccinated must provide proof of vaccination and/or evidence of anti-PV immunity prior to enrollment, as applicable.
• Ability to safely discontinue anti-coagulant therapy(ies) prior to biopsy/catheter placement, as required per site/surgical guidelines.
• Hemoglobin ≥ 9 g/dL prior to biopsy/catheter placement.
• Platelet count ≥ 100, 000/μL (unsupported); ≥ 125,000/ μL (can be supported via platelet transfusion) at biopsy/catheter placement.
• Absolute Neutrophil Count (ANC) ≥ 1000/μL prior to biopsy/catheter placement.
• Creatinine ≤ 1.2 x Upper Limit of Normal (ULN) prior to biopsy/catheter placement.
• Total bilirubin, Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) ≤ 2.5 x ULN prior to biopsy/catheter placement.
• Prothrombin time (PT) and activated Partial Thromboplastin Time (aPTT) ≤ 1.2 x ULN prior to biopsy/catheter placement.
• If undetectable antitetanus toxin (ATT) Immunoglobulin G (IgG) at screen, Tdap booster vaccine ≥ 1 week prior to biopsy/catheter placement.
• Patients must be willing and able to understand and provide written informed consent.

Exclusion Criteria

• Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) ≤ 12 weeks prior to lerapolturev infusion (Note: does not apply for patients treated with pembrolizumab under this protocol who are eligible for lerapolturev retreatment). Note: patients who had previously permanently discontinued any anti-PD-1 or PD-L1 therapy due to severe or life-threatening immune-related adverse events are excluded.
• Excluded are:
• Neoplastic lesions in the brainstem, cerebellum, or spinal cord.
• Radiological evidence of active/growing multifocal disease: no size increase > 0.5 cm in any direction of any other enhancing non-targe