Lerapolturev (PVSRIPO) in GBM

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Age ≥ 18 years old at the time of entry into the study.
• Histopathologically confirmed recurrent supratentorial glioblastoma (WHO grade 4) (high grade glioma with molecular features of glioblastoma will be eligible).
• Karnofsky Performance Score (KPS) ≥ 70%
• Hemoglobin ≥ 9 g/dl prior to biopsy
• Platelet count ≥ 100,000/µl unsupported is necessary for eligibility on the 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.
• Neutrophil count ≥ 1000 prior to biopsy
• Creatinine ≤ 1.5 x normal range prior to biopsy
• Total bilirubin ≤ 1.5 x ULN prior to biopsy (Exception: Participant has known or suspected Gilbert's Syndrome for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
• AST/ALT ≤ 2.5 x ULN
• Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy. Patients with prior history of thrombosis/embolism are allowed to be on anticoagulation, understanding that anticoagulation will be held in the perioperative period per the neurosurgical team's recommendations. Low molecular weight heparin (LMWH) is preferred. If a patient is on warfarin, the international normalized ratio (INR) is to be obtained and value should be below 2.0 prior to biopsy.
• At the time of biopsy, prior to administration of the 1st infusion of lerapolturev via CED, the presence of recurrent tumor must be confirmed by histopathological analysis.
• Able to undergo brain MRI with and without contrast
• Prior CDC-recommended vaccination series against PV and has received a boost immunization with trivalent Poliovirus Vaccine Inactivated (IPOL®) (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to administration of lerapolturev. Note: Patients who are unsure of their prior vaccination status must provide evidence of anti-PV immunity prior to enrollment, as applicable.
• Patient or partner(s) meets one of the following criteria:
• Non-childbearing potential (i.e., not sexually active, physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile, or any male who has had a vasectomy). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study is defined as 1 year without menses.; or
• Childbearing potential and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g., a condom or diaphragm) used with spermicide.
• A signed informed consent form approved by the Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study

You cannot join if

• Females who are pregnant or breast-feeding
• Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate
• Patients with severe, active co-morbidity, defined as follow:
• Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C)
• Patients with known immunosuppressive disease or known human immunodeficiency virus infection
• Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
• Patients with known lung (forced expiratory volume in the first second of expiration (FEV1) < 50%) disease or uncontrolled diabetes mellitus
• Known albumin allergy
• History of agammaglobulinemia
• Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks [except for nitrosourea (6 weeks), or metronomic dosed chemotherapy such as daily etoposide or cyclophosphamide (1 week)] prior to starting the study drug unless patients have recovered from side effects of such therapy
• 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 have received treatment with tumor treating fields (e.g., Optune®) ≤ 1 week prior to starting the study drug
• Patients may not be less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation
• Patients who have not completed all standard of care treatments, including surgical procedure and radiation therapy (Please note: For patients under 65 years old, standard radiation therapy is typically at least 59 Gy in 30 fractions over 6 weeks. For patients 65 years or older, standard RT is often reduced to a minimum 40 Gy in 15 fractions over 3 weeks.)
• If the MGMT promoter in their tumor is known to be unmethylated, patients are not mandated to have received chemotherapy prior to participating in this trial
• If the MGMT promoter in their tumor is known to be methylated or the MGMT promoter methylation status is unknown at time of screening, patients must have received at least one chemotherapy regimen prior to participating in this trial
• Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of active (growing) disease (active multifocal disease); extensive subependymal disease (tumor touching subependymal space is allowed); tumor crossing the midline or leptomeningeal disease
• Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the 1st lerapolturev infusion via CED
• 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
• Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months
• Patients with known history of hypersensitivity to lomustine, dacarbazine, or any components of lomustine

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

lerapolturev. A recombinant, live attenuated, nonpathogenic oncolytic virus containing the oral poliovirus Sabin type 1 in which the internal ribosomal entry site (IRES) is replaced with the IRES from human rhinovirus type 2 (HRV2), with potential antineoplastic activity. Upon administration of lerapolturev, the poliovirus is selectively taken up by and replicates in tumor cells expressing CD155 (poliovirus receptor, PVR or NECL5) eventually causing tumor cell lysis. Following the lysis of infected cells, the replicated virus is released and can infect adjacent cells, which both induces further tumor cell oncolysis and may activate, through the release of tumor-associated antigens (TAAs) and inflammatory mediators from the lysed tumor cells, the immune system to mount an anti-tumor immune response. This further kills tumor cells. This may also stimulate long-term anti-tumor immunity. Additionally, lerapolturev can induce a systemic anti-tumor immune response through engagement with antigen-presenting cells (APCs) upon CD155 binding thereby further killing tumor cells. CD155, an oncofetal cell adhesion molecule and tumor antigen, is ectopically expressed in certain cancers, such as glioblastoma multiforme (GMB), and plays an important role in tumor cell migration, invasion, and metastasis. Due to the heterologous HRV2 IRES in this recombinant virus, lerapolturev only propagates in susceptible CD155-expressing, nonneuronal neoplastic cells. NCI Drug Dictionary

Treatments listed in the registry

• Lerapolturev (Drug): Lerapolturev (intratumoral) will be dosed at 2x108 TCID50 in 3.0 mL x 2 doses (total dose 4x108 TCID50) by Convection Enhanced Delivery. For the patients randomized to the lerapolturev Arm 1 of Stage 2, seven days (±2 days) following completion of the 2nd intratumoral infusion of lerapolturev, patients will begin cervical perilymphatic subcutaneous injection of lerapolturev at a dose of 2 x 108 TCID50 (in 0.5 ml diluent) around the cervical lymph node chain ipsilateral to the intracranial tumor.
• Lomustine Pill (Drug): Lomustine will be given as a single oral dose of 110 mg/m2 every six weeks for up to 9 cycles.

Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• biopsy: Part of the study plan
• MRI: Part of the study plan
• surgery: Part of the study plan

Main goals

• Proportion of patients at each dose level who experienced a dose-limiting toxicity - Stage 1 (Up to 1 year)
• Proportion of patients who experience an unacceptable toxicity - Stage 2 (Up to 1 year)
• Overall survival (OS) - Stage 2 (2 years)

Other goals

• Progression free survival (PFS)

Planned enrollment: 92 (estimated).

• Duke University Medical Center, Durham, North Carolina

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06177964
• NCI Drug Dictionary: C184921

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Jul 19, 2026. Public record; not medical advice.