Lerapolturev in Recurrent Malignant Glioma

This is a Phase 2 study of lerapolturev, an oncolytic polio/rhinovirus recombinant, in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma. The objective of this study is to investigate the safety and efficacy (anti-tumor response and survival) of lerapolturev in recurrent WHO grade IV malignant glioma.

Patients will be administered lerapolturev intratumorally via convection-enhanced delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. Retreatment with lerapolturev is allowed, provided retreatment eligibility criteria are met.

Inclusion criteria

SUMMARY:

• Patients must have a recurrent (first or second recurrence only, including this recurrence; transformation from a lower grade tumor to a WHO grade IV malignant glioma will be considered a first recurrence) supratentorial WHO grade IV malignant glioma based on imaging studies with measurable disease (a minimum measurement of 1 cm and maximum of 5.5 cm of contrast-enhancing tumor) with prior histopathology consistent with a WHO grade IV malignant glioma confirmed by the site's neuropathologist or the neuropathologist's designate.
• Male patients who are sexually active are eligible if he and/or his partner(s) meets the criteria outlined in the protocol. Female subjects are eligible if he and/or his partner(s) meets the criteria outlined in the protocol.
• Age ≥ 18 years of age.
• Karnofsky Performance Status (KPS) Score ≥ 70%.
• Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.
• Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy.
• Neutrophil count ≥ 1000 prior to biopsy.
• Hemoglobin ≥ 9 prior to biopsy.
• Platelet count ≥ 100,000/μL unsupported is necessary for eligibility on study; however, because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/μL is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion.
• Creatinine ≤ 1.2 x normal range prior to biopsy.
• Positive serum anti-PV titer prior to biopsy.
• The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week, but less than 6 weeks, prior to administration of the study agent.
• At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis.
• A signed IRB-approve informed consent form (ICF).
• Able to undergo brain MRI with and without contrast.

Exclusion criteria

SUMMARY:

• Females who are pregnant or breast-feeding.
• Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons, their designate, and the reviewer designated by the sponsor.
• Patients with severe, active co-morbidity, defined as in the protocol.
• Patients with a previous history of neurological complications due to PV infection.
• Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used.
• Patients may not have received tumor treating fields (≤ 1 week), chemotherapy or bevacizumab ≤ 4 weeks [except for nitrosourea and lomustine (≤ 6 weeks); metronomic dosed chemotherapy, such as daily temozolomide, etoposide or cyclophosphamide (≤ 1 week)] prior to starting the study drug.
• Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy.
• Patients may not be less than 12 weeks from radiation therapy of the brain, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation.
• Prior to enrollment, has not completed all standard of care treatments, including surgical procedure and radiation therapy (at least 59Gy) as outlined in the protocol.
• Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of multiple areas of active (growing) disease (active multifocal disease); tumors with contrast-enhancing tumor component crossing the midline (crossing the corpus callosum); extensive subependymal disease (tumor touching subependymal space is allowed); or extensive leptomeningeal disease (tumor touching leptomeninges is allowed).
• Patients with undetectable anti-tetanus toxoid immunoglobulin G (IgG).
• Patients with known history of agammaglobulinemia.
• Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to admission for lerapolturev infusion.
• Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups).
• Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin.
• For patients randomized prior to V7, a known history of hypersensitivity to lomustine, dacarbazine, or any components of lomustine.
• Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.