Lerapolturev in Recurrent Malignant Glioma

NCT02986178 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00077024
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Malignant Glioma

Keywords

Glioblastoma; Glioma; PVSRIPO; Duke; Pro00077024; Brain tumor; Istari; Recurrent; GBM; rGBM

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Objective Radiographic Response

  Assess objective anti-tumor response based on iRANO criteria.

  up to 5 years

• Duration of Objective Radiographic Response

  Assess time of confirmed response to confirmed disease progression or death

  up to 5 years

Secondary Outcomes (4)

• Median Overall Survival

  up to 5 years

• Landmark Survival

  at 24 and 36 months post-lerapolturev infusion

• Disease Control Rate

  up to 5 years

• Safety of Lerapolturev

  up to 52 weeks

Study Arms (2)

lerapolturev

EXPERIMENTAL

lerapolturev administered once intratumorally by convection-enhanced delivery

Biological: lerapolturev

lerapolturev + lomustine

EXPERIMENTAL

lerapolturev administered once intratumorally by convection-enhanced delivery plus one dose of lomustine at 8 weeks post-lerapolturev dosing

Biological: lerapolturev; Drug: Lomustine

Interventions

lerapolturev BIOLOGICAL

A single dose of lerapolturev, an oncolytic polio/rhinovirus recombinant

Also known as: PVSRIPO

lerapolturev; lerapolturev + lomustine

Lomustine DRUG

one cycle of oral lomustine

Also known as: gleostine

lerapolturev + lomustine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify 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, 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.

Sponsors & Collaborators

• Istari Oncology, Inc.: lead
• Duke University: collaborator

Study Sites (6)

UCSF Neurological Surgery

San Francisco, California, 94941, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Preston Robert Tisch Brain Tumor Center at Duke University

Durham, North Carolina, 27710, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• Brown MC, Beasley GM, McKay ZP, Yang Y, Desjardins A, Randazzo DM, Landi D, Ashley DM, Bigner DD, Nair SK, Gromeier M. Intratumor childhood vaccine-specific CD4+ T-cell recall coordinates antitumor CD8+ T cells and eosinophils. J Immunother Cancer. 2023 Apr;11(4):e006463. doi: 10.1136/jitc-2022-006463.

  PMID: 37072349 DERIVED

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke University

MeSH Terms

Conditions

Glioma; Glioblastoma; Brain Neoplasms; Recurrence

Interventions

Lomustine

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Istari Oncology

info@istarioncology.com

919-245-7662

Study Officials

• Head of Clinical Operations

  Istari Oncology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Study began as parallel (randomized two arm study) and was revised to single group.

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: December 8, 2016
• Study Start: June 1, 2017
• Primary Completion: September 30, 2022
• Study Completion: February 3, 2023
• Last Updated: July 11, 2025
• Results First Posted: July 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)